# Fileset

[ChemSci.24_15_18715.pdf](https://mdr.nims.go.jp/filesets/5071c54f-deea-4d28-a285-7f38997c4e98/download)

## Creator

[Jingwen Song](https://orcid.org/0000-0003-1910-9287), [Anna Jancik-Prochazkova](https://orcid.org/0000-0002-6193-3694), [Kohsaku Kawakami](https://orcid.org/0000-0002-3466-9365), [Katsuhiko Ariga](https://orcid.org/0000-0002-2445-2955)

## Rights



## Other metadata

[Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science](https://mdr.nims.go.jp/datasets/8cd1de1d-fdae-4a8b-a25c-d1e6785fef19)

## Fulltext

Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical scienceChemicalScienceREVIEWLateral nanoarchJingwen SongJdTP2SW(M(M2aMNaResearch Center for Functional Materials, N(NIMS), 1-1 Namiki, Tsukuba 305-0044, IbabResearch Center for Materials NanoarchitecScience (NIMS), 1-1 Namiki, Tsukuba 305-0nims.go.jpCite this: Chem. Sci., 2024, 15, 18715Received 20th August 2024Accepted 26th October 2024DOI: 10.1039/d4sc05575frsc.li/chemical-science© 2024 The Author(s). Published byitectonics from nano to life:ongoing challenges in interfacial chemical scienceJingwen Song,a Anna Jancik-Prochazkova, b Kohsaku Kawakami acand Katsuhiko Ariga *bdLateral nanoarchitectonics is a method of precisely designing functional materials from atoms, molecules,and nanomaterials (so-called nanounits) in two-dimensional (2D) space using knowledge ofnanotechnology. Similar strategies can be seen in biological systems; in particular, biological membranesingeniously arrange and organise functional units within a single layer of units to create powerfulsystems for photosynthesis or signal transduction and others. When our major lateral nanoarchitecturalapproaches such as layer-by-layer (LbL) assembly and Langmuir–Blodgett (LB) films are compared withbiological membranes, one finds that lateral nanoarchitectonics has potential to become a powerful toolfor designing advanced functional nanoscale systems; however, it is still rather not well-developed witha great deal of unexplored possibilities. Based on such a discussion, this review article examines thecurrent status of lateral nanoarchitectonics from the perspective of in-plane functional structureorganisation at different scales. These include the extension of functions at the molecular level by on-surface synthesis, monolayers at the air–water interface, 2D molecular patterning, supramolecularpolymers, macroscopic manipulation and functionality of molecular machines, among others. In manysystems, we have found that while the targets are very attractive, the research is still in its infancy, andmany challenges remain. Therefore, it is important to look at the big picture from different perspectivesin such a comprehensive review. This review article will provide such an opportunity and help us seta direction for lateral nanotechnology toward more advanced functional organization.ingwen Song received her PhDegree from The University ofokyo under the guidance ofrofessor Katsuhiko Ariga in021. She also studied in theupermolecules Group at theorld Premier InternationalWPI) Research Centre foraterials NanoarchitectonicsMANA), National Institute foraterials Science (NIMS) from018 to 2021. She is currentlypostdoctoral researcher in theedical So Matter group,IMS.Anna Jancik-ProchazkovaAnna Jancik-Prochazkovareceived her PhD in materialschemistry from the BrnoUniversity of Technology (BUT),Czech Republic, in 2019. Shejoined the Advanced FunctionalNanorobots Laboratory at theUniversity of Chemistry andTechnology (UCT) Prague whereshe worked in the eld of nano-robotics. Since 2023, she hasbeen a JSPS postdoctoralresearch fellow at the Super-molecules Group at the NationalInstitute for Materials Science (NIMS), Japan. Her current researchfocuses on single atom decorated nanorobotics for environmentalremediation.ational Institute for Materials Scienceraki, Japantonics, National Institute for Materials044, Japan. E-mail: ARIGA.Katsuhiko@cGraduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1Tennodai, Tsukuba 305-8577, Ibaraki, JapandGraduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwa-no-ha, Kashiwa 277-8561, Japanthe Royal Society of Chemistry Chem. Sci., 2024, 15, 18715–18750 | 18715http://orcid.org/0000-0002-6193-3694http://orcid.org/0000-0002-3466-9365http://orcid.org/0000-0002-2445-2955http://crossmark.crossref.org/dialog/?doi=10.1039/d4sc05575f&domain=pdf&date_stamp=2024-11-18Chemical Science Review1. IntroductionThe development of materials science is crucial for pushing thefrontiers in modern society. Fabrication of advanced functionalmaterials is of paramount importance when revolutionizingtechnologies that affect the daily life of humanity. Materialsscience is especially needed in developing sustainable energyproduction1 and storage systems2 (such as solar cells,3 fuelcells,4 batteries,5 and supercapacitors,6 among others), materialconversion through catalysts,7 hydrogen production,8 sensors,9devices,10 environmental purication technologies,11 and lastbut not least medical applications,12 i.e. drug delivery,13 tissueengineering, etc.14Designing new functional materials is not limited only tochemical processes to fundamentally produce new materialswith desired properties. Emphasis must be placed on thecontrol of their supramolecular structure as well. During thelong history of development, we have learned that it is extremelyimportant to control not only the substance itself but also itsnanostructure.15 This major trend has grown dramatically sinceRichard Feynman initiated the rise of nanotechnology in themiddle of the 20th century.16 Nanotechnology enabled obser-vation of nanoscale objects,17 creation of nanostructures,18 andevaluation of their physical properties.19 This technology hashad a huge impact on the world of materials science. Thedevelopment of functional materials was no longer possiblewithout considering the nal nanostructures; this gave rise tothe great eld of nanoarchitectonics – a post-nanotechnologysuccessor to nanotechnologies.20 Nanoarchitectonics and itsprinciples were rst proposed by Masakazu Aono at the begin-ning of the 21st century21 as a method of designing functionalmaterials from atomic and molecular nano-units with theknowledge of nanotechnology (Fig. 1).22 A similar concept isoen used in self-assembly processes in supramolecularchemistry,23 the creation of metal–organic frameworks (MOF) incoordination chemistry,24 the preparation of covalent organicframeworks (COF) in polymer chemistry,25 and templatesynthesis in materials science.26 In terms of science and tech-nology, it is desirable to treat these concepts as a unied eldrising from general scientic pillars. Therefore, it can be saidKohsaku KawakamiKohsaku Kawakami received hisPhD in chemical engineering in2000 from Kyoto University.Aer working for pharmaceu-tical companies including Shio-nogi and Merck, he joined theNational Institute for MaterialsScience in 2006. He is currentlya group leader of the MedicalSoMatter group and a directorof the Material Open Platformfor Pharmaceutical Science. Healso serves as a professor at theUniversity of Tsukuba.18716 | Chem. Sci., 2024, 15, 18715–18750that nanoarchitectonics is not a novel approach but an incor-poration of multiple concepts into one general eld. In otherwords, nanoarchitectonics aims to integrate a wide range ofdisciplines within the nanoeld.27 The general principles ofnanoarchitectonics are not limited only to the eld of materialchemistry; they overlap with many other elds, such as micro-fabrication techniques, biochemical methods, and others,making it easy to design complex, asymmetric and hierarchicalstructures regardless of the chosen material or application.28Not limited to non-covalent interactions commonly seen insupramolecular assembly, material construction in nano-architectonics approaches includes material expansionsthrough covalent bonding. The concept of nanoarchitectonics isexpanding from fundamental elds such as physics,29 chem-istry,30 and biology31 to applied elds such as energy conver-sion,32 sensors,33 devices,34 and environmental,35 andbiomedical applications.36 Since matter is fundamentally madeup of atoms and molecules organized within space in a denedand organized way, nanoarchitectonics is a methodology thatapplies to all matter. If the ultimate goal of physics is to eluci-date the theory of everything,37 analogously, the goal of nano-architectonics could be to achieve a method for everything inmaterials science.38The method of skillfully organizing unit structures andassembling advanced functions is seen in living organisms.Functions such as photosynthesis and signal transduction arethe result of the sophisticated arrangement and organization offunctional units.39 The goal of nanoarchitectonics is to designthese structures and material systems articially.40 Biologicalsystems have achieved the art of functional organizationthrough trial-and-error learning over billions of years. We aretrying to achieve this articially in the last few decades, sincepostulating the principles of nanotechnologies. From this pointof view, it is a very tough and complex challenge. Perhaps therst step should be to target the architecture of a local func-tional organization in 2D space, which is the main goal oflateral nanoarchitectonics. Lateral nanoarchitectonics assists inthe design, fabrication, and characterization of functional 2Dstructures with dened properties on a macroscopic level.Precise control of the atomic and molecular organization isKatsuhiko ArigaKatsuhiko Ariga received hisPhD degree from the TokyoInstitute of Technology in 1990.He joined the National Institutefor Materials Science (NIMS) in2004 and is currently the leaderof the Supermolecules Groupand a senior scientist withspecial missions of ResearchCentre for Materials Nano-architectonics (MANA), NIMS.He is also appointed asa professor in The University ofTokyo.© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 1 Nanoarchitectonics approach: (A) outline of the nanoarchitectonics concept; (B) vertical nanoarchitectonics for controlled layeredorganization carried out with well-known techniques such as the Langmuir–Blodgett film; (C) lateral nanoarchitectonics for controlled orga-nization within the 2D plane as the main subject of this review discussed with a variety of objects.Review Chemical Sciencetypically achieved at the interface environment.41 Architectingfunctional materials at the interface is a realistic yet simpliedapproach in a two-dimensional (2D) space. When we under-stand the general principles of nanoarchitectonics in such 2Dsystems, the path of organizing functions in a wide three-dimensional (3D) space will be clearer. Commonly used nano-architectonics methods applying interface science are theLangmuir–Blodgett (LB) method42 and layer-by-layer (LbL)assembly.43 These methods create skillfully dened layeredstructures and achieve functional coordination between them atthe atomic and molecular levels.Comparing the latter methodology with functional organi-zation in biomembranes, a signicant difference is observed.While the LB and LbL methods build layered functional struc-tures, biomembranes sophisticatedly arrange and organizefunctional units within two-dimensional assemblies. This isa more advanced level of interfacial nanoarchitectonics ach-ieved by living organisms. Humans have made many examplesof rational stacking and functionalization of layered structuresby applying the principles of nanoarchitectonics. Yet, theconstruction of complex functional structures within a singleplane still has a lot of mechanisms to understand and chal-lenges to overcome. Therefore, the frontier in forming complexadvanced functional structures lies here in lateralnanoarchitectonics.Here, we review the lateral structural architectures of variousfunctional systems projecting the general principles of lateralnanoarchitectonics into each example. The examples presented© 2024 The Author(s). Published by the Royal Society of Chemistryare not necessarily selected from well-developed researchsubjects. We examine the degree of development by referring notonly to recent examples of research, but also to examples fromseveral decades ago. In this review, we will discuss the followingtopics, depending on the size and complexity of the structure: (i)lateral relay activity of molecules and molecular machines ona solid, (ii) Langmuir system: structure formation, (iii) Langmuirsystem: formational regulation between molecules and bulk, and(iv) Langmuir and liquid interfacial systems: emerging chal-lenges, (v) on an aqueous membrane, and (vi) living cells at theliquid interface. These include extending molecular level func-tions by on-surface synthesis, monolayers at the air–water inter-face, formation of supramolecular receptors, 2D molecularpatterning, macroscopic manipulation of molecular machines,collective functions of molecular rotors, coupled functions ofbiomolecular machines, and many more. By considering variousinterfaces, the current and future development of lateral nano-architectonics is assessed. We believe that this review article willprovide such an opportunity and help us nd new ground-breaking directions in lateral nanoarchitectonics towardadvanced functional material organization.2. Lateral relay activity of moleculesand molecular machines on a solidMolecular lateral nanoarchitectonics postulates the mostfundamental principles at the level of individual molecules thatChem. Sci., 2024, 15, 18715–18750 | 18717Chemical Science Revieware crucial for understanding more complex systems. In thissection, we summarize the lateral structural extensions andfunctional linkages and their visualization on the molecularlevel.2.1. Covalent approachAtomic and molecular-level nanoarchitectonics on 2D surfaceshas been studied in combination with probe microscopy.44 Forexample, an array of diacetylene derivatives adsorbed ona surface can be stimulated with the tip of a probe microscopeto form polydiacetylene molecular wires at the desired loca-tions.45 There is also an example of using a probe microscope toselectively induce longitudinal oligomerization at a speciclocation on an array membrane consisting of several molecularlayers of C60 molecules.46 Stimulated and unstimulated loca-tions can be distinguished at the molecular level in 2D space.This technique can create arbitrary molecular-level resolutionpatterns resulting in the formation of 2D barcodes in a 2Dplane. Another example is the use of a chip that can activatesurface molecules by removing individual bromine atomsallowing a subsequent surface reaction with fullerene mole-cules.47 In the latter example, an organic reaction can occur atthe desired position of the molecule on the surface. Thisapproach is called local probe chemistry.48 Thus, lateral nano-architectonics with molecular-level resolution can be developedby controlling organic synthesis on surfaces. Examples of suchresearch took place especially in the research eld of surfacesynthesis.49 In the following paragraphs, we will discuss somerecent examples of this trend.Graphene nanoribbons are promising candidates for next-generation nanoelectronics.50 These structures can be laterallyconstructed for more advanced nanoarchitectures. In partic-ular, graphene nanoribbon heterojunctions have attracteda great deal of attention because they exhibit exotic topologicalelectronic phases at the heterointerface. Ma, Feng, and co-workers synthesized graphene nanoribbon heterojunctionsfrom block polyphenylene precursors by chain growth poly-merization (Fig. 2).51 First, precursors of heterojunctions with N= 9 armchair graphene nanoribbon segments and chevrongraphene nanoribbon segments were synthesized. In the nextstep, cyclodehydrogenation of the block polyphenyleneprecursor resulted in the formation of graphene nanoribbonheterojunctions. The process was analysed in situ by scanningtunneling microscopy (STM) at the molecular level. The gra-phene nanoribbon heterojunctions, which combine units withdifferent topologies, enable novel electronic band structureengineering. It can provide new topological electronic states atthe interface. Exotic topological states are useful for quantuminformation processing devices and spintronics. The strategy ofprojecting lateral nanoarchitectonics into the fabrication ofnovel graphene nanoribbon heterostructures will providemolecularly designable carbon materials for applications inadvanced nanoelectronics devices.Single-molecule current rectiers are fundamental buildingblocks of organic electronics. Friedrich, Pascual, and co-workers reported a study of tuneable current rectication18718 | Chem. Sci., 2024, 15, 18715–18750through a designed graphene nanoribbon.52 The extraordinarycurrent rectication efficiency was achieved by doping seven-unit graphene nanoribbons with one unit of diboron ona gold substrate with atomic precision. Quantum transportthrough suspended boronated graphene nanoribbons betweenthe STM tip and the surface was investigated (Fig. 3). Monopolarresonant transport via a boron-induced in-gap state embeddedin graphene nanoribbons was examined. The presence of theboron moiety conned the valence band, while a quantum-wellstate was formed in the ribbon. Both the ground and excitedstates of the quantized bands supported the resonant transportof electrons, which enabled efficient in situ tuneable currentrectication. The asymmetric position of the quantum dotswithin the ribbon was comparable to that of the current recti-cation of asymmetric two-level molecules. This example ofmolecular nanoarchitectonics represents an innovativeapproach to precisely manipulate the functionality of molecularelectronic states. It opens new avenues for advanced applica-tions in organic electronics.2.2. Supramolecular approachFunctional propagation between molecules arranged ina supramolecular non-covalent arrangement in a 2D plane hasalso been investigated. For example, Heinrich, Lutz, and co-workers demonstrated molecular cascades by organizingcarbon monoxide molecules on a copper(111) surface withatomic precision using low-temperature STM.53 In their model,the motion of one molecule triggered the motion of another,resulting in a domino-like cascade motion at temperaturesbelow 6 K. Here, the hopping motion of the carbon monoxidemolecules occurred as a result of the quantum tunneling of themolecules between adjacent sites on the surface. The tunnelingrate was controlled by adjusting the direction of hopping andinteractions with neighbouringmolecules. Devices such as logicgates were created by placing molecules at the intersections ofthe cascade to design multiple AND and OR gates. Overall, theability to control the direction and speed of molecular motiondemonstrated the potential for extremely small logic circuits.Interlocking molecular machines laterally in a 2D plane hasalso been demonstrated. This is the creation of molecular gearsthat move in tandem by bringing multiple molecular rotors intolateral contact in a 2D plane. Gears are universal mechanicalelements used in many elds; not only are they key componentsin basic mechanisms of technology, such as clocks and motors,but they are also essential components of machines that oper-ate in harsh environments, such as nuclear power plants andouter space. General requests are to minimize the energyrequired for such amachine to function and to reduce its weightfor portability. To achieve this, it is imperative that the gears beas small as possible. To this end, molecular gears were fabri-cated using single-molecule manipulation by STM. The trans-mission of rotation along the gear train is an essentialprerequisite for the construction of molecular mechanicalmachines. Soe et al. reported the interlocking structure of twoand three molecular hexa-tert-butylbiphenylbenzene gears ona superconducting Pb(111) surface (Fig. 4).54 The gears were© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 2 On-surface synthesis of graphene nanoribbon heterojunctions from block polyphenylene precursors by chain-growth polymerization:chemical reaction (top) and molecular-level imaging by in situ scanning tunnelling microscopy (bottom). Reproduced under terms of the CC-BYlicense from ref. 51, 2023 Wiley-VCH.Fig. 3 Measurement of quantum transport through borylated graphene nanoribbons suspended between the STM tip and the surface: bottomimage, structure of a borylated ribbon segment and STM topography imagewhere the red cross indicates the position fromwhere the ribbonwaslifted. Reproduced under terms of the CC-BY license from ref. 52, 2024 Wiley-VCH.Review Chemical Sciencedesigned and synthesized with long biphenyl teeth. To mini-mize the mechanical entanglement between the gears thathinders the transmission of the rotation along the gear train,the advantage of the native monatomic steps on the Pb(111)surface was used. When each molecular gear was placed in the© 2024 The Author(s). Published by the Royal Society of Chemistryinterlocking train at a different monatomic step height on thesupport surface, a functioning long molecular gear train wasconstructed. Other measures include designing long, rigidmolecular teeth. Alternatively, the interaction between therotating elements and the surface can be reduced by elevatingChem. Sci., 2024, 15, 18715–18750 | 18719Fig. 4 Interlocking structure of three hexa-tert-butylbiphenylbenzene molecular gears on a superconducting Pb(111) surface at a differentmonatomic step: (left) chemical structures of integrated gears and (right) STM images of train motions of the interlocked gears. Reprinted withpermission from ref. 54 Copyright 2020 American Chemical Society.Chemical Science Reviewthe gears on the anchor unit. It can be concluded thata sophisticated molecular design is crucial for the interaction ofmolecular rotors.It is advantageous for the molecular gear to be equipped witha specic group that facilitates the tip–molecule interaction toenhance the manipulation by STM. Such a marker alsoenhances the evaluation of rotational behaviour. Therefore,Moresco and co-workers attached a tert-butyl group on the endof the tooth of one of the gears (Fig. 5).55 With this design,reproducible stepwise rotation of a single gear was achieved. Itwas also ensured that the rotation of up to three interlockingunits could be transmitted: operating the tert-butyl tooth of thethird gear as a driver at the tip of the STM; an incidentalbehaviour was created in the transmission of rotation betweenFig. 5 (Left) a molecular gear with a tert-butyl group on the tooth; (right)to two followers triggered by the tip of the STM at the driver gear. RepriSociety.18720 | Chem. Sci., 2024, 15, 18715–18750the three meshing gears. A sequence of rotational transmissionalong a gear train connecting three molecules was as follows:when a molecule rotated counterclockwise from the driver,a follower molecule rotated 75° clockwise. Simultaneously,another follower molecule rotated 78° counterclockwise. A next-level challenge is the development of a molecular mechanicalcalculator; the nanoarchitectonics and controllability ofrotating a large number of gears in the interlocking train will becrucial for this purpose.In this section, we have shown several examples of lateralnanoarchitectonics at the molecular level. Through the exten-sive connection of the desired molecular units to the on-surfacesynthesis, highly organized structures can be created, allowingthe individual molecules to act as electronic devices.the rotation transmission of three interlocking units from the driver gearnted with permission from ref. 55 Copyright 2020 American Chemical© 2024 The Author(s). Published by the Royal Society of ChemistryReview Chemical ScienceAlternatively, a mechanism in which molecular gears move intandem holds great potential for creating ultrasmall machinery.Further development of these approaches will give rise to tinymechanical parts with a degree of modication at the molecularlevel, which is currently at the very basic stage of research. It isclear that these examples represent novel and challengingresearch elds. The lateral architecture of molecules and theirassemblies will lead to the development of a wide variety ofmolecular technologies in this direction. Many of these exam-ples require both nanotechnology techniques, such as STMobservation and molecular metrology, and knowledge of tradi-tional organic synthesis. This is a typical style of nano-architectonics approach, i.e., the fusion of nanotechnology andexisting materials science.3. Langmuir system: structureformationThe examples discussed in the last section illustrate how lateralnanoarchitectonics and precise molecular positioning, ach-ieved through techniques such as STM, can lead to the creationof highly organized molecular systems and functional deviceson solid surfaces. However, molecular positioning and organi-zation are not limited to solid surfaces. In fact, Langmuirsystems provide another powerful approach for constructingordered molecular layers at liquid interfaces. Similar to thecontrol achieved through STM on solid substrates, Langmuirsystems allow for the deposition of well-dened molecularlayers with nanoscale precision. Moreover, more dynamiclateral functional links occur in membrane structures, such aslipid bilayers in aqueous solution or Langmuir monolayers onaqueous surfaces.56 In this section, we will give some charac-teristic examples of lateral nanoarchitectonics in Langmuirsystems, focusing on the fabrication of specic structures.3.1. Biomimic lipid ra modelA functional lateral structure with a particular arrangement andclustering of molecules within the lipid monolayer in a bio-membrane is called a lipid ra.57 It can be thought of as lateralnanoarchitectonics in lipid membranes that takes place natu-rally. Lipid ras are liquid-ordered phases that are islands ofordered lipids that coexist within a liquid-disordered phase.Lipid ras are responsible for many functions of the membrane.Their precise nature and molecular structure are being investi-gated with great interest. Using the lipid ra model, it becameclear that the specic molecular arrangements of the phospho-lipid aggregates in the membrane are deeply involved in physi-ological functions. For example, the relationship between lipidras and the function of proteins incorporated into them is ofinterest. To study most membrane proteins, their insertion intolipidmembranes is necessary to fully understand their propertiesand activity. The successful reconstitution of a protein in a lipidramodel membrane depends on the lateral nanoarchitectonicsof the membrane.As an example of a lipid ra model, Bilewicz and co-workersexamined the incorporation of a protein 3-hydroxy-3-© 2024 The Author(s). Published by the Royal Society of Chemistrymethylglutaryl coenzyme A reductase (HMG-CoA reductase)into the mimetic membrane of the lipid ra.58 This enzyme isa transmembrane glycoprotein located on the membrane of theendoplasmic reticulum and is responsible for cholesterolbiosynthesis in hepatocytes. Model lipid membranes composedof 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol(Chol), and sphingomyelin (SM) in a 1 : 1 : 1 molar ratio weredesigned to reproduce lipid systems with compositions andsurface properties that mimicked lipid ras. The Langmuirmonolayer, formed by spreading liposomes and proteoliposomesat the air–water interface, was used as a thin lipid ramembranemodel to measure reductase activity and monitor statin inhibi-tion. The Brewster angle microscopy images recorded aerspreading the liposomes indicate the coexistence of the phases aswell as phase separation. It was conrmed that the activity of thereductase membrane wasmaintained over time in the ramodelmembrane at the air–water interface. Furthermore, the inhibi-tion process was monitored by changing the concentration of thecomponents of the catalytic reaction. Such studies of membraneproteins in lipid ra model environments are well suited forinvestigating the underlying mechanisms of lipid–protein inter-actions. It also provides a model system to understand the effectsof other molecules on protein activity.Analyses of the in-plane structure of lipid ra models alsoprovide an assessment of the in-plane structures that spontane-ously form in lateral nanoarchitectonics. Studies of condensedislands in lipid ras have shown a wide range of sizes andmorphologies, suggesting substantial in-plane molecularanisotropy and mesoscopic structural chirality. Thämer and co-workers used phase-resolved sum-frequency generation micros-copy to analyse micrometre-scale condensed domains of mixed-chirality model phospholipid monolayers in 3D space (Fig. 6).59In the reported approach, the C–H stretching vibrations of thephospholipid molecules were directly probed. To investigatemolecular packing and interactions, monolayers of (R)/(S)-dipal-mitoylphosphatidylcholine and fully deuterated (unsaturated) 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine mixed in a 4 : 1 ratiowere fabricated. Hyperspectral images of differentdipalmitoylphosphatidylcholine-rich domains of the membranewere observed. This imaging technique combined the spectro-scopic selectivity to distinguish molecular species with the abilityto detect the absolute molecular orientation encoded in thesignal phase. The domains showed a curved molecular orienta-tion with helical mesoscopic packing. Both the molecularorientation and helical rotation direction depended on thechirality of the lipid. Different enantiomeric mixtures formedstructures that deviated from the mirror symmetry. These factsindicated strong enantioselectivity in the domain growth process.In other words, a fundamental thermodynamic differencebetween homochiral and heterochiral membranes was indicated.This advance in microscopic vibrational imaging offers prom-ising prospects for further studies of lipid ras.3.2. Associated receptor and 2D molecular patternLipid ras, which are formed by the lateral aggregation of lipidsin the membrane plane, are interesting biochemical targets.Chem. Sci., 2024, 15, 18715–18750 | 18721Fig. 6 Phase-resolved sum-frequency generation microscopy to analyze micron-scale condensed domains of phospholipid monolayers ofmixed chirality as a lipid bilayer raft in 3D space. Reproduced under terms of the CC-BY license from ref. 59, 2024 Springer-Nature.Chemical Science ReviewNot only natural lipids, but articially synthesized amphiphilicmolecules have also been used in lateral nanoarchitectonics togenerate functional structures by specically assembling themin a 2D plane. For example, complex molecular sites can becreated by lateral nanoarchitectonics on aqueous interfaces.Receptor proteins and enzymes have molecular recognitioncavities in which peptide residues are precisely organized.However, articially reconstructing such active structures isoen a very challenging task. Amphiphilic molecules withrelatively simple peptide residues and amphiphilic moleculeswith various functional groups can be assembled in the Lang-muir membrane plane to create sophisticated receptor struc-tures in nanoarchitectonics.60Fig. 7 shows an example of an equimolar monolayer con-sisting of a dioctadecylglycylglycinamide amphiphile and anamphiphile functionalized with guanidinium groups.61 In thismixed monolayer, the optimal recognition structure was spon-taneously formed by molecular assembly in the presence ofa water-soluble dipeptide (Gly–Leu). Langmuir isotherm anal-ysis of the binding behaviour of Gly–Leu to this mixed mono-layer showed that the binding site of a single Gly–Leu moleculewas formed cooperatively by the two monolayer components.The binding constant was 6400 M−1 which was higher than thebinding constant for the monolayer of the glycylglycinamideamphiphile alone. This means that simple functional groupsassembled on a supramolecular basis can show great capabilitythrough their cooperative action. When benzoate amphiphileswere used as mixed components instead of functional amphi-philes with guanidinium groups, the binding constantsdecreased. Obviously, the guest binding efficiency was regulatedby the component molecules being nanoarchitectonized. It isimportant to create a suitable conguration state of the hostfunctional group for strong hydrogen bonding with the guest.Such a lateral nanoarchitectonics approach has the great18722 | Chem. Sci., 2024, 15, 18715–18750advantage of being able to accommodate the recognition ofdiverse guests by changing the functional groups of thecomponents and their combinations. In particular, the highbinding efficiency demonstrated here could lead to the sensitivedetection of a wide variety of aqueous peptides. This trans-formation should be useful for sensing physiologically impor-tant peptides, such as peptide hormones and neuropeptides.Since hydrogen bonding plays an essential role, the systemcould be applied to other types of biologically important guests.For example, nucleotide mimics can create recognition domainpeptide structures on the surface of monolayers for enzymecofactors. Model systems could be designed for the recognitionof sugars by lectins or gangliosides by hemagglutinin.It was experimentally62 and theoretically63 proven thatmolecular recognition by molecular interactions such ashydrogen bonding is stronger at the air–water interface than inthe bulk aqueous phase. In addition to the recognition ofpeptides already discussed, molecular recognition at the air–water interface has been reported for sugars,64 amino acids,65nucleobases,66 and nucleotides.67 When water-soluble guestmolecules with multiple different moieties or functional groupsare used, the corresponding amphiphiles for recognition maybe bound separately at each location. In other words, a singlewater-soluble guest molecule can specically interact withdifferent types of membrane components. This ability allowedthe creation of a 2D molecular pattern with a specic moleculararrangement on the surface of the monolayer.68 As shown inFig. 8, water-soluble avin adenine dinucleotides had multiplecomplementary hydrogen bond recognition sites. As a result,multisite molecular recognition occurred at the air–waterinterface. In this case, guanidinium and orotate amphiphileswere used as recognition host molecules. Mixed monolayers ofthese amphiphilic molecules were transferred onto mica andtheir surfaces were observed by atomic force microscopy (AFM).© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 7 Associated receptor at the air–water interface: an equimolar mixed monolayer of a dioctadecylglycylglycinamide amphiphile anda functional amphiphile with guanidinium groups for the optimal recognition structure of a water-soluble dipeptide (left: guest molecules andright: green labels).Review Chemical ScienceThe monolayers transferred from pure water showed a surfaceof uniform height and a periodic hexagonal pattern consistingof only one type of methyl peak. On the other hand, the AFMimage of the mixedmonolayer transferred from a avin adeninedinucleotide solution showed a periodic pattern consisting oftwo methyl peaks of different heights. The 2D molecularpatterning of the latter resulted from the rearrangement of themonolayer components based on specic recognition by theavin adenine dinucleotide template molecule. Throughbinding of the avin adenine dinucleotide to the mixedmonolayer, the recognition functional groups of the twoamphiphilic molecules were placed at the same height. ThisFig. 8 2D molecular pattern with a specific molecular arrangement in tdinium and orotate amphiphiles with water-soluble flavin adenine dinuca flavin adenine dinucleotide solution with a periodic pattern consisting© 2024 The Author(s). Published by the Royal Society of Chemistryresulted in a height difference between the terminal methylgroups of the two amphiphilic molecules. The 2D arrangementof the interacting groups in the template molecule was trans-lated into a height pattern of alkyl chains. This observation isproof that lateral nanoarchitectonics can effectively target anappropriate molecular design of templates to organize regularlyrepeating patterns in various monolayers.3.3. Supramolecular polymer and gel berSupramolecular polymers are a class of polymer-like materialsin which individual building units assemble non-covalently viaintermolecular forces such as hydrogen bonding, p–phe monolayer surface: (left) multisite molecular recognition of guani-leotide; (right) an AFM image of the mixed monolayer transferred fromof two methyl peaks of different heights.Chem. Sci., 2024, 15, 18715–18750 | 18723Chemical Science Reviewinteractions, and others.69 Koyano et al. developed a supramo-lecular polymer at the air–water interface by deployinga monolayer of long-chain dialkylmelamine in an aqueousbarbituric acid solution (Fig. 9).70 The surface pressure–molec-ular area (p–A) isotherms indicated that long-chain dia-lkylmelamine (2-amino-4,6-di(dodecylamino)-1,3,5-triazine)molecules created well-packed monolayers at the air–waterinterface. When the aqueous phase contained barbituric acid,the molecular area increased and barbituric acid moleculeswere inserted to form a supramolecular polymer. Supramolec-ular polymer formation was monitored with infrared (IR)spectroscopy by focusing on the signals of hydrogen bondsbetween long-chain dialkylmelamines and barbiturates. Thebinding constant of barbituric acid to long-chain dialkylmel-amine monolayers was large enough at 3000 M−1, providing thenecessary stiffness of the resulting supramolecular polymers.The structure of the monolayer transferred to mica wasobserved by AFM. The monolayers transferred from the puremonolayer were fragile and unsuitable for observation.However, long-chain dialkylmelamine monolayers transferredfrom barbituric acid solution onto mica plates were observed byAFM, showing a regular arrangement of the terminal methylgroups. This method of forming supramolecular polymers bythe association of two components at the air–water interfacecan be utilized with a variety of combinations of components,and it therefore represents a powerful tool for lateralnanoarchitectonics.Marchi-Artzner et al. investigated the behaviour of hydrogen-bonded supramolecular polymers of 2,4,6-triaminopyrimidineand barbituric acid linked to tetraoxyethylene spacers at the air–water interface.71 In this case, the resulting supramolecularpolymer possessed a exible structural design because of thepresence of tetraoxyethylene spacers between the hydrogen-bonding functional group and the alkyl chain. The behaviourof the supramolecular polymer at the air–water interface wasinvestigated using uorescence microscopy in addition to p–Aisotherms, AFM, FT-IR, and XPS. The effects of pH and ionicFig. 9 Supramolecular polymer at the air–water interface: (left) chemamino-4,6-di(dodecylamino)-1,3,5-triazine) molecules with aqueous bapolymers on a mica surface showing that the terminal methyl groups ar18724 | Chem. Sci., 2024, 15, 18715–18750strength of the aqueous phase were also investigated. Inparticular, the latter results indicated an electrostatic contri-bution from the acid–base properties of 2,4,6-triaminopyr-imidine and barbituric acid in addition to hydrogen bondinginteractions. The results showed that the formation of supra-molecular polymers was highly efficient in the presence of tet-raoxyethylene spacers. Moreover, it can be generalized that theuse of spacers provides the resulting structures with exibilityand freedom in their design and functionalization.Rather than specifying a rigid structure at the interactionsite, as in supramolecular polymers, lateral nanoarchitectonicscan be advanced at the air–water interface through moreambiguous and exible molecular associations. Kumaki and co-workers synthesized star-shaped poly(L-lactide) with 2–12 armsby polymerizing L-lactide with various polyols as initiators toinduce crystalline behaviour in monolayers (Fig. 10).72 As sup-ported by AFM analysis, poly(L-lactide) crystallized by formingextended chain crystals in Langmuir monolayers. The advan-tage of analysing the monolayers was in the fact that the chainpacking was characterized by determining the thickness of thelamellae. On spreading double-stranded poly(L-lactide) on thesurface of water in a diluted state, isolated chains oated at theair–water interface. Upon compression, the two poly(L-lactide)chains rst formed a condensed amorphous monolayer.Subsequently, the two poly(L-lactide) chains crystallized intofolded lamellae with central diol units aligned in the samedirection. Crystallization proceeded via a condensed amor-phous state. Poly(L-lactide) consisting of two to four arms crys-tallized with all arms aligned in the same direction and foldedwith a central polyol unit. On the other hand, poly(L-lactide)consisting of 6 and 12 arms crystallized with half of both armsextending in opposite directions from the centre. This wasprobably due to steric obstacles in the crowded arms. In bothsystems, the poly(L-lactide) arms showed a strong tendency tocrystallize in the same direction. Such observations and theelucidation of the general trend are important for lateralical structures of the supramolecular polymer of dialkylmelamine (2-rbituric acid; (right) an AFM image of the transferred supramoleculare regularly arranged.© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 10 AFM images of extended chain crystals of the synthesized star-shaped poly(L-lactide) with 2–12 arms in Langmuir monolayers where twopoly(L-lactide) chains then crystallize into folded lamellae with a central diol unit aligned in the same direction. Reprinted with permission fromref. 72 Copyright 2023 American Chemical Society.Review Chemical Sciencenanoarchitectonics at the air–water interface using a variety ofpolymers.Gels are formed when small molecules aggregate to formlong-range structures. In gels, self-assembled one-dimensional(1D) bers incorporate solvent and form 3D structures.73Specically, a linear p-gelator self-assembles into an entangledber withmolecules aligned perpendicular to the long axis of theber. However, with this general approach, it is difficult to orientthe gelator molecules parallel to the long axis of the 1D structure.Lateral nanoarchitectonics at the air–water interface can offera suitable solution. Sakakibara et al. aligned nanorods composedof oligo(p-phenylenevinylene)-derived p-gelators at the air–waterinterface and studied the molecular orientation within thealigned rods (Fig. 11).74 The nanorods were 340 ± 120 nm inlength and 34 ± 5 nm in width and showed the orientation ofoligo(p-phenylenevinylene) molecules parallel to the long axis ofthe rods. Upon increasing surface pressure, the rods aligned inone direction to ll the voids in the monolayer effectively. Near-eld scanning optical microscopy revealed that local photoexci-tation led to different excited-state properties. Polarized uo-rescence spectra of the aligned rods showed marked anisotropy.The polarization intensity ratio (parallel/perpendicular) was 2.4.Interestingly, this was completely opposite to the uorescencepolarization measurements of the alignment of entangled bersof oligo(p-phenylenevinylene)-type gels made in solution, whichshowed a strong uorescence intensity in the vertical direction.Long-range excitation energy transfer occurred in the entangled© 2024 The Author(s). Published by the Royal Society of Chemistrybers of solution gels, causing uorescence quenching. Incontrast, uorescence was greatly enhanced in nanorods alignedat the air–water interface. The overall results demonstrated thatentangled gel bers with vertically alignedmolecules are suitablefor excitation energy transfer, while nanorods with a parallelalignment of molecules are suitable for charge transport. Inchromophore supramolecular assemblies, the packing mode ofmolecules at the nanoscale is an important factor that controlsthe photophysical and energy transport processes of excitedstates. Understanding the mechanism of excitation energytransfer in 1D molecular assemblies may help design supramo-lecular structures with improved charge transport properties.Lateral nanoarchitectonics at the air–water interface can yieldefficient functional structures.In this section, we introduced several examples of lateralnanoarchitectonics at the air–water interface, focusingprimarily on structure creation. The freedom of motion at theair–water interface and the limited extent of spreading allowedfor specic 2D nanoarchitectonics. Its effective importance isexemplied by the biochemical role of lipid ras. Molecularrecognition at the interface can create patterns with molecular-level structural precision. Long-range specic structures can bebuilt by crystallization of polymers and alignment of gel bers.Although perhaps inferior to molecular nanoarchitectonics onsolid surfaces in terms of structural accuracy and specicity, theair–water interface is a very promising venue for lateral nano-architectonics with long-range extensions.Chem. Sci., 2024, 15, 18715–18750 | 18725Fig. 11 Controlled 1D assemblies with different internal molecular orientations: (top) entangled fibers processed in solution; (bottom) alignednanorods assembled at the air–water interface. Reprinted with permission from ref. 74 Copyright 2014 American Chemical Society.Chemical Science Review4. Langmuir system: formationalregulation between molecules andbulkThe air–water interface is a very specic functional environ-ment, given its dimensionality and asymmetry of motion. In thelateral direction, the air–water interface extends macroscopi-cally, and its motion is at the visual level. On the other hand, inthe thickness direction, it is closed at the molecular level. Theliquid interface, including the air–water interface, bridges themolecular level and macroscopic phenomena in terms of bothstructures and functions.75 This section will focus on macro-scopic and molecular functional regulation.4.1. Functional regulation from macro to moleculeThe molecular machines operating at the air–water interfaceattract a great deal of attention.76 Frank, Stoddart, and co-workers built a so-called molecular shuttle at the air–waterinterface.77 In their work, the molecular shuttle was derivedfrom a rotaxane structure, as shown in Fig. 12. The stationaryrecognition sites consisted of units of tetrathiafulvalene and1,5-dioxynaphthalene rings. A tetracationic cyclophane, cyclo-bis(paraquat-p-phenylene), served as the shuttle. The amphi-philic structure suitable for operating at the air–water interfacewas given by the choice of stopper. The end close to the tetra-thiafulvalene unit was a hydrophobic tetraarylmethane stopper,while the end close to the 1,5-dioxynaphthalene ring unit wasterminated by a hydrophilic tetraarylmethane stopper, repre-senting an amphiphilic bistable [2]rotaxane-type molecularshuttle. Using Langmuir lm balance, the effects of varyingcompression rate and subphase temperature were investigated.Analysis of Langmuir lms and LB lms transferred onto Sisubstrates suggested that the rotaxane existed in a skeletalconformation at an acute angle to the air surface or to thesurface. The pronounced hydrophilicity allowed the cyclophane18726 | Chem. Sci., 2024, 15, 18715–18750to be tightly bound to the subphase, resulting in a folded ortilted conformation. The creation of such molecular super-structures will have important implications for molecular elec-tronic devices based on bistable amphiphilic [2]rotaxanes.As an environment for driving molecular machines, the air–water interface provides a uniquemedium. Molecular machinesare typically driven by irradiation of light, heat energy, chemicalreactions, and redox reactions. These external sources stimulatethe molecules which induce the propulsion of molecularmachines. On the other hand, achieving the propulsion ofmolecular machines by applying mechanical stimuli is chal-lenging. The only way to directly touch a molecule is to bring itinto contact with a tip of a probe microscope. If macroscopicmechanical stimuli, such as hand motions, are to be trans-mitted to molecules, controlled molecular machines can beoperated by hand-motion-like actions. When macroscopicmechanical stimuli such as compression and expansion areapplied to monolayers on the air–water interface, the moleculesin the monolayer can deform mechanically in response. Inlateral nanoarchitectonics at the air–water interface, molecularmachines are arranged as monolayers and macroscopicmechanical stimuli can be used to manipulate the molecularmachines within the monolayer.78 Since mechanical manipu-lation is induced macroscopically, typically by hand movement-like stimuli, this technology is referred to as hand-operatingnanotechnology.79A representative example is shown in Fig. 13.80 The presentedmolecular machine was derived from steroid cyclophane; inparticular, it consisted of a cyclic core of 1,6,20,25-tetraaza[6.1.6.1]paracyclophane with four cholic acids linked by a ex-ible L-lysine spacer. When the steroid cyclophane was deployedas a monolayer at the air–water interface, it took on a spreadingconformation with the hydrophilic part of the cholic acid on thewater surface. When this monolayer was mechanicallycompressed, the arms bent and took on a cavity-type confor-mation. During this change, guest molecules in the aqueous© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 12 The molecular shuttle with the stationary recognition sites of a tetrathiafulvalene unit and a 1,5-dioxynaphthalene ring unit and a tet-racationic cyclophane, cyclobis(paraquat-p-phenylene), as the shuttle at the air–water interface. Reprinted with permission from ref. 77Copyright 2004 American Chemical Society.Fig. 13 A structure of steroid cyclophane consisting of a cyclic core of 1,6,20,25-tetraaza[6.1.6.1]paracyclophane with four cholic acids linked inits monolayer to exhibit capability of reversible guest molecule capture by external mechanical forces.Review Chemical Sciencephase were trapped. Capture and release of the guest werereversibly repeated and controlled by manipulating the molec-ular machine by macroscopic mechanical mutation. Langmuirmonolayers at the air–water interface represent excellent eval-uation media because they can be easily compressed andexpanded while monitoring molecular area and surfacepressure.Not only such dynamic conformational changes, but subtleconformational tuning of receptor molecules is also possible atthe air–water interface. Fig. 14A shows polycholesterylsubstituted cyclen complexes organized into monolayers asreceptor molecules to investigate the binding of amino acids inthe aqueous phase.81 The receptor monolayer was an aggregate© 2024 The Author(s). Published by the Royal Society of Chemistryof chiral molecules and the binding of chiral amino acidsresulted in diastereomer formation. The enantioselectivity wassuccessfully reversed in the molecular recognition of aminoacids by macroscopic lateral pressure. When the monolayer wascompressed, the binding constants of the amino acidsincreased, and, in the case of valine, a reversal of chiral selec-tivity from the D- to the L- form was observed. The selectivity ofthe monolayers varied with slight differences, depending on thestructure of the amino acid: a feature comparable to the delicatefunction of enzymes and receptors in living organisms. Asimilar methodology was applied to one of the most challengingbiomolecular recognition problems, namely the discriminationbetween thymine and uracil (Fig. 14B).82 The design andChem. Sci., 2024, 15, 18715–18750 | 18727Fig. 14 Mechanical tuning of various molecular receptors at the air–water interface: (A) polycholesteryl-substituted cyclen complexes for chiralrecognition of aqueous amino acids; (B) cholesterol-armed triazacyclononan for discrimination between thymine and uracil derivatives; (C)receptor for indicator displacement assay of glucose binding with controls of Förster resonance energy transfer (FRET). Reprinted withpermission from ref. 81 Copyright 2006 American Chemical Society, ref. 82 Copyright 2010 American Chemical Society, and ref. 83 Copyright2012 Wiley-VCH.Chemical Science Reviewsynthesis of enzyme-like articial hosts for this purpose isextremely difficult. Using a Langmuir monolayer at the air–water interface, a simple receptor molecule was mechanicallyadapted to determine the optimal point of molecular recogni-tion. Cholesterol-armed triazacyclononan was used as the18728 | Chem. Sci., 2024, 15, 18715–18750receptor molecule, and its Langmuir monolayer wascompressed in the absence and presence of Li+ cations forstructural tuning. Under optimized conditions, uracil recogni-tion was achieved approximately 64-fold more selectively thanthat of thymine. Furthermore, the indicator displacement assay,© 2024 The Author(s). Published by the Royal Society of ChemistryReview Chemical Scienceone of the sensing strategies, was applied to the Langmuirmonolayer system (Fig. 14C).83 This approach took advantage ofthe phenomenon of competitive binding of the indicator andguest to complementary sites on the receptor molecule.Mechanical compression was applied to the receptor monolayerat the interface to facilitate the indicator displacement assay.The Förster resonance energy transfer (FRET) between thereceptor and the indicator was switched on by this compres-sion; the addition of D-glucose displaced the indicator andeffectively quenched the FRET process. The guest concentrationwas inferred by measuring the ratio of uorescence intensitiesin situ. Such a link between functional groups in a monolayer isundoubtedly an important clue for the future development oflateral nanoarchitectonics.In many instances, the molecular recognition mode wasconsidered uniquely with reference to a stable structure such asthe crystal structure. However, the addition of the element ofdynamically searching for the optimal structure can bring outthe potential of the receptor molecule. Molecular recognitionbegan with the primary recognition of guests by host moleculessuch as crown ethers and cyclodextrins.84 This is the basis ofsupramolecular chemistry. A mode of switching selectivity byisomerization of the host was incorporated later.85 In fact, mostcurrent molecular machines are based on this switching ofstable states.86 The interface-based method presented heretunes between a myriad of states to nd the optimal structure.87Organic molecules are known for their exibility; to think ofthem uniquely in terms of a crystal-like structure or to consideronly a few states is not a legitimate use of their potential.Organic molecules can demonstrate their potential capabilitiesby continuously changing their structures and tuning theirfunctional properties. For this purpose, it is necessary to tunethe molecular structure mechanically. It is envisioned as aneffective method to link macroscopic behaviour with molecularfunctions in an interfacial environment.4.2. Functional regulation from molecule to macroAs demonstrated in the above example, the Langmuir mono-layer system can couple macroscopic phenomena with those atthe molecular level. In situ lateral nanoarchitectonics isimportant for function expression. The above example con-verted macroscopic mechanical stimuli into recognition func-tions at the molecular level. Conversely, it is also possible toaccumulate molecular-level stimuli at the liquid interface (notFig. 15 Coherent collective precession of molecular rotors with chiral p© 2024 The Author(s). Published by the Royal Society of Chemistrynecessarily at the air–water interface), which can inducephenomena at the macroscopic level.Synthetic molecular motors are subject to thermal uctua-tions. For this reason, they are likely to be unable to performuseful functions on their own. Amechanism is needed to amplifythe motion of a single molecule to a level that is distinguishablefrom the thermal background. Condensing molecular motorsinto so-ordered phases such as interfacial lms or liquid crys-tals is a possible approach to solve it. Tabe and Yokoyamainvestigated the coherent collective precession of molecularrotors with chiral propellers using liquid crystalline phases at theliquid interface (Fig. 15).88 Here, a condensed layer of molecularrotors was developed at the glycerol–air interface. The monolayerconsisted of simple rod-like molecules with chiral propellers. Asa chiral liquid crystal monolayer, it underwent coherent molec-ular precession driven by the transmembrane movement ofwater molecules. As a result, spatiotemporal patterns of molec-ular orientation were observed. Interestingly, reversing either themolecular chirality or the direction of water molecule movementreversed the direction of rotation associated with the switch fromexpansion to convergence of the target pattern. Thus, a liquidcrystalline phase with only so-directional order was evaluatedas the optimal medium to assist molecular motors in manifest-ing their individual motion in a collective manner. In principle,the constituent chiral molecules were supposed to rotate in theow eld, even when isolated. However, they tended to be over-whelmed by thermal noise because their molecular masses werenot large enough to sufficiently overcome the thermal amplitude.Cooperative motion, as shown here, amplied the ne individualmolecular motion to macroscopic scales. This paves the way forlateral nanoarchitectonics in the design of articial motilemolecular systems.Żywociński, Hołyst, and co-workers reported the collectiveprecession of molecular rotors on liquid surfaces.89 The effect ofthe molecular structure was studied on Langmuir monolayersof four ferroelectric liquid crystals. In two of them, only polargroups were attached to the water surface, with the chiralgroups located well above the interface of the elongated mole-cules. In the other two ferroelectrics, the polar and chiral groupswere in close proximity, so that the chiral groups were alsoattached to the water surface or submerged in water. Compar-ative experiments showed that the system exhibited collectiverotation induced by water evaporation only when the chiralgroups of the ferroelectric liquid crystals in the Langmuirropellers using liquid crystalline phases at the liquid interface.Chem. Sci., 2024, 15, 18715–18750 | 18729Chemical Science Reviewmonolayer were not attached to the interface and remained inair. In contrast to the linear ow of water, the collectiveprecession behaviour was closely related to the position of thechirality centre relative to the air–water interface. In otherwords, molecular nanoarchitectonics, which is perpendicular tothe interface, can control the collective precession that developslaterally. Cooperative rotation is an example where individualmolecular motions are amplied to the mesoscale.Molecular motion can also be detected as macroscopic wavepropagation at the interface. Tabe et al. reported photoinducedtravelling waves in condensed liquid crystalline Langmuirmonolayers composed of azobenzene derivatives.90 The pre-sented system was studied using simultaneous microscopy,which enabled the detection of the tilt and azimuthal compo-nents of themolecular orientation separately. The dependence ofwave generation and propagation on excitation power, symmetryconditions, temperature, and molecular density was determinedfor azobenzene compounds. Nonequilibrium dynamic patternswere observed in ordinary uids, semiconductors, and chemicalreaction systems in solution and on solid surfaces. In contrast tothese classical systems, the reported travelling waves in photo-excitable condensed Langmuir monolayers played an essentialrole in the pattern formation process because of short-rangeintermolecular interactions. The rod-shaped molecules in theirmonolayer were coherently tilted from the layer normal. Theywere irradiated with weak light to induce trans–cis photo-isomerization. Spatiotemporal periodic oscillations of themolecular azimuthal angles propagated as a 2D azimuthal wave.This wave formation took place at the asymmetric interface,where the lm exhibited a broken vertical symmetry. This waveformation occurred only when the chromophore was continu-ously excited near the long wavelength end of its absorption, andphotoisomerization was repeated between the trans and cisforms. This wave was associated with periodic rotation of theazimuthal angle of the molecule and was not accompanied by tiltvibrations. Langmuir monolayers composed of various azo-benzene derivatives exhibited similar travelling waves withvelocities proportional to the excitation power. For the wave topropagate over long distances, it had to undergo frequentconformational changes between the trans and cis states whilemaintaining an average cis ratio of a few percent. As a result, thecoupling between the anisotropy of the excitation and thebreaking of symmetry with respect to the lm plane plays amajorrole in determining the direction of the wave.In the above two sections, we explored the possibilities oflateral nanoarchitectonics, focusing on functions in the Lang-muir system. A characteristic feature of the series of systemswas the coupling of molecular motion with macroscopic func-tions and properties. At so, 2D interfaces with degrees offreedom, the macroscopic and the nano-phenomena arecoupled. In a sophisticated system such as a monolayer on anaqueous surface, the evaluation of such a system is easier thanin a 3D system. At present, the functionality is limited to thelevel of nano-macro coupling, but the pursuit of lateral func-tional linkage represents a pioneering challenge. ControllingFRET phenomena by 2D mechanical compression and the18730 | Chem. Sci., 2024, 15, 18715–18750propagation of molecular motion as waves can be taken as earlyexamples in this direction.5. Langmuir and liquid interfacialsystems: emerging challengesLangmuir and liquid interfacial systems also provide variousopportunities for emerging sciences. For example, attemptshave been made to create metal–organic frameworks (MOFs)91and covalent organic frameworks (COFs)92 in a liquid interfaceenvironment. This can be seen as an example of the applicationof lateral nanoarchitectonics extending the regular structurehorizontally. Another example where lateral nanoarchitectonicscan help to elucidate crucial mechanisms is in the eld of nano-and microrobotics. Nano- and microrobots are autonomousnano/microscopic objects that possess propulsion abilities andare able to perform given tasks.93 Such emerging challenges willbe introduced in detail in this section. Some of the examplesmay not be directly related to nanoarchitectonics. However,such examples are inclusively described here for possibilities inemerging and future challenges.5.1. Interfacial MOF and COFThe synthesis of ultrathin MOF lms and their rationalassembly can yield highly ordered microporous materials witha well-controlled growth direction and lm thickness. Theenvironment at the liquid interface provides exibility and highcontrollability necessary for nanoarchitecting the MOF struc-tures.94 Makiura, Kitagawa, and co-workers reported the nano-architectonics of fully preferentially oriented MOF nanolmscomposed of metalloporphyrins at room temperature (Fig. 16).95In their work, the LB method with complex chemistry wascombined to prepare MOF ultrathin lms. The combination ofvarious modular processes represented a typical approach ofnanoarchitectonics. MOF lms consisting of 2D sheet incor-poratedmetal-coordinated pyridinemolecules were prepared bydeveloping 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrinato-cobalt(II) and pyridine in a solution of CuCl2$2H2O inchloroform/methanol. The principles of lateral nano-architectonics enabled the formation of 2D MOF sheets thatwere subsequently transferred onto a substrate. In the next step,the principles of vertical nanoarchitectonics allowed fora sequential LbL stacking to form a highly organized multilay-ered lm consisting of metalloporphyrin building blocks andmetal-ion junctions. This was a nice example of the combina-tion of lateral and vertical nanoarchitectonics that led to theproduction of MOF nanolms of arbitrary thickness. It is worthnoting that these nanoarchitectonics strategies are versatile,and it would be possible to stack individual layers of differenttypes of MOFs to obtain complex ordered heterostructures. Thisnanoarchitectonics methodology is suitable for creating heter-ostructures with smooth interfacial junctions and will bea powerful method for obtaining integrated device systems.Single molecule magnets are an attractive target for memorydevice fabrication since they are able to dramatically increaseinformation storage capacity. Regular arrays of single molecule© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 16 MOF monolayers obtained by developing 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrinato-cobalt(II) and pyridine on a solution ofCuCl2$2H2O in chloroform/methanol that is multilayered by a sequential LbL stacking procedure. Reprinted with permission from ref. 95Copyright 2010 Springer-Nature.Review Chemical Sciencemagnets must be constructed on a substrate for facile access toindividual single molecule magnets. To meet this requirement,Horii and co-workers fabricated a MOF nanosheet-based singlemolecule magnet by applying the principles of lateral nano-architectonics.96 The single molecule magnet consisted of Tb3+sandwiched between 5,10,15,20-tetrapyridylporphyrinato andphthalocyaninato ligands. Phthalocyaninato-porphyrinato-ter-bium(III) double-decker single molecule magnets reacted withPd2+ ions at the air-liquid interface upon the formation ofregularly and preferentially oriented mechanically robust MOFnanosheets. X-ray magnetic circular dichroism measurementsrevealed that the MOF sheets exhibited perpendicular magneticanisotropy. It had signicant advantages in the high concen-tration of single molecule magnets and in the regularity of thestructure. In addition, compared to conventional methods interms of substrate-independent structures, this approach seemsto be convenient and highly efficient; it holds great potential forthe construction of molecular magnetic memory devices.2D COFs are crystalline polymers with a lattice-like structurethat have been applied for the fabrication of energy storagedevices and water purication systems. Similar to the prepara-tion of MOF structures, COFs can be efficiently synthesized withthe assistance of nanoarchitectonics. Matsumoto et al. reporteda method for forming COFs at the oil–water and air–waterinterfaces (Fig. 17).97 In particular, imine-bonded COFs wereobtained by interfacial polymerization of 1,3,5-tris(4-aminophenyl)benzene and terephthalaldehyde monomersusing Sc(OTf)3, a Lewis acid catalyst. Sc(OTf)3-catalyzed poly-merization proceeded rapidly at room temperature with a lowcatalyst loading. The critical advantage of using the principlesof lateral nanoarchitectonics was in the fact that the© 2024 The Author(s). Published by the Royal Society of Chemistryaccumulation of the catalyst and monomer at the interfaceinduced site-selective polymerization, which led to the forma-tion of a continuous COF lm. Moreover, there were fewerdesign constraints on the monomer, such as the need todissolve the monomer in different phases. Continuous COFlms of large area (several cm2) were obtained with the thick-ness ranging from 100 mm to 2.5 nm. The large area, controlledpore size, and tuned molecular composition were evaluated tobe promising for nanoltration applications. The COFmembranes were transferred to polyethersulfone supports andtested for water purication from model organic contamina-tion. The interfacial polymerization of imine-bound COFs withSc(OTf)3 shown here is expected to be applicable for the prep-aration of other functional COF thin lms, such as electroni-cally active COFs.Lateral nanoarchitectonics at the interface is not the onlyapproach toward the synthesis of COFs. Jiang and co-workersreported the preparation of electronically active multicompo-nent COFs in a fully liquid environment (Fig. 18).98 Thesynthesis was based on multicomponent [1 + 2] and [1 + 3]condensation systems using one knot and two or three linkerunits. The resulting hexagonal and square multicomponentCOFs comprised asymmetrically tiled organic units that formedanisotropic frameworks and peculiarly shaped pores. Yaghi andco-workers applied the principles of nanoarchitectonics tosynthesise imine-bonded COFs by combining hex-aaminophenylbenzene, tetragonal tetrakis(4-aminophenyl)ethane, and trigonal 1,3,5-tris(p-formylphenyl)benzene.99 Asa result, 2D COFs with unprecedented topology were obtained.The incorporation of three different types of linkers of differentconnectivities within the 2D COFs enabled precise control of theChem. Sci., 2024, 15, 18715–18750 | 18731Fig. 17 COFs with imine bonding obtained by interfacial polymerization of 1,3,5-tris(4-aminophenyl)benzene and terephthalaldehyde asmonomers using Sc(OTf)3, a Lewis acid catalyst, resulting in nanoarchitectonics of a continuous COF film at the interface. Reprinted withpermission from ref. 97 Copyright 2018 Elsevier.Chemical Science Reviewresulting geometry; the multicomponent COF had three types ofvertices and two types of edges. This high degree of complexitycan extend the range of 2D COF structures. By developing sucha multicomponent COF structure with the assistance of lateralnanoarchitectonics at the interface, it will be possible to createfunctional systems that develop rational functional coordina-tion within a 2D plane. It is expected that the vectorial transferof electrons and the aggregation of information and energy willbecome possible.5.2. Microrobot working on a water surfaceApart from the approach in which rational structures are con-structed at the 2D interface using lateral nanoarchitectonics tolink functions, systems with functional autonomous objectspropelled freely within the 2D surface are interesting as well.Candidates for such systems are nano- and microrobots thatoperate in an interfacial environment.100The design and development of nano-, micro-, andmillimeter-scaled autonomous systems capable of motion in anFig. 18 COF synthesis based on multicomponent condensation systemsBY license from ref. 98, 2016 Springer-Nature.18732 | Chem. Sci., 2024, 15, 18715–18750interfacial environment using various driving forces haveattracted great attention. Pumera and co-workers developeda polymer capsule motor that was independent of externalenergy and studied its coordinated behaviour on the watersurface (Fig. 19).101 The small millimeter-sized robot waspropelled on the water surface without consuming any externalenergy or external fuel such as H2O2 or glucose. The drivingforce of the propulsion was an asymmetric release of organicsolvent from the capsule. This resulted in an asymmetricchange in the surface tension of the surrounding liquid. Themolecular capsule motor moved toward the direction of highsurface tension due to the Marangoni effect, trying to reach thedesired lowest free energy state. The self-driven polymer capsuleused here was fabricated by dropping a polysulfone solution inN,N0-dimethylformamide onto the surface of an aqueous liquid.When the polysulfone molecules interacted with water, theyunderwent a phase transition and solidied at the interfacewhile forming small pores within the structure. N,N0-dime-thylformamide was then slowly and asymmetrically releasedwith different component ratios. Reproduced under terms of the CC-© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 19 Polymer capsule motor running on a liquid surface upon asymmetric changes in the surface tension of the surrounding liquid due to theMarangoni effect. Photos on the left side demonstrate oil droplet pushing by the capsule motor. Reprinted with permission from ref. 101Copyright 2011 Wiley-VCH.Review Chemical Sciencefrom the capsule to the solution/air interface through the pores,leading to self-propulsion abilities through a variety of liquid/air interfaces, including water, seawater, organic solvent/watermixtures, and acids. This property is useful in environmentalapplications. It is envisioned to clean up oil spills and toxicchemicals released into the environment.Oil removal is undoubtedly a hot topic in environmentalremediation. Jancik-Prochazkova et al. developed magneticallynavigated indigo-based hydrophobic microrobots for oilremoval (Fig. 20).102 The microrobots were fabricated by con-verting leucoindigo to insoluble indigo in the presence ofcommercially available spherical magnetic Fe3O4 nanoparticles.As a result of strong inter- and intramolecular hydrogen bondsand p–p interactions, indigo formed microparticles that wereinsoluble in water and common organic solvents. The presenceof magnetic nanoparticles enabled wireless navigation in anexternal magnetic eld. Moreover, a swarming behaviour wasobserved in a laterally rotating magnetic eld. Due to theirhydrophobic nature, the microrobots entered and subsequentlyFig. 20 Magnetic navigation of indigo-based hydrophobic microrobotsactual operation for oil removal. Reprinted with permission from ref. 102© 2024 The Author(s). Published by the Royal Society of Chemistrytransported oil contamination in a controlled way, enabling itsremoval from the aqueous environment.In this section, we present some new challenges in research,mainly at the air–water interface. The Langmuir system is notall about the traditional approach of assembling and aligninglipid-like molecules. Liquid interfaces allow coordinationchemistry and macromolecular chemistry to be deployed withrestricted dimensions to create 2D COFs and MOFs. Theincorporation of multiple components and step-by-step crea-tion by employing the principles and tools of lateral nano-architectonics represents the next stage in the development offunctional materials for a new era of electronic devices, solu-tions for environmental remediation, and beyond.6. On aqueous membranesIn the previous sections, we considered solid interfaces withatomic resolution and air–water interfaces of clean monolayer-level thickness as suitable environments for developing lateralfor oil removal: (left) preparation method and working principle; (right)Copyright 2022 American Chemical Society.Chem. Sci., 2024, 15, 18715–18750 | 18733Chemical Science Reviewnanoarchitectonics. In this section, we take biological systems asa model for the lateral organization of functional molecules andtheir interactions. Therefore, we will focus on lateral nano-architectonics in lipid bilayers and membrane systems. Ingeneral, lipid bilayers and membranes are more dynamic unitsthan those formed over solid surfaces or air–water interfacesbecause of their disordered structure. Their ability to immobilizefunctional elements, such as biomolecules, presents a very usefuland interesting environment for functional coordination.103 Inthe following sections, we will discuss lateral nanoarchitectonicsat aqueous membrane interfaces, including lipid bilayers.6.1. DNA nanotubes and DNA origamiMedia such as lipid bilayers have a high affinity for biologicalcomponents, and the use of DNA aggregates as a mediatoroffers huge possibilities. DNA nanotechnology allows a highdegree of design and assembly of complex structures.104 Exam-ples of the application of DNA nanotubes and DNA origami tolateral nanoarchitectonics on membrane surfaces in anaqueous solution are presented below.A longstanding challenge in biotechnology is to rationallyconstruct articial channels in cell membrane models.105 Thegoal is to engineer synthetic nanopores that allow selectiveaccess to the interior of the cell through the lipid bilayer. Onepromising methodology is to embed DNA nanotubes into lipidbilayers. Joshi and Maiti analysed the stability and dynamics ofsix-helical tiled DNA nanotubes embedded in a 1-palmitoyl 2-oleoyl-sn-glycero-3-phosphocholine lipid bilayer in 0.2 ms longequilibrium.106 Lipid molecules in close proximity to DNAnanotubes reoriented to form a toroidal structure (Fig. 21). Thehead groups of lipid molecules near the membrane lumencooperatively leaned toward the hydrophilic sugar–phosphatebackbone of the DNA. As a result, the formation of a toroidalstructure around the patch of DNA nanotubes protruding intothe membrane was observed. This mechanism reduced the freeenergy barrier for the formation of the porous lumen of DNAnanotubes in the lipid bilayers. The energy barrier wasFig. 21 All-atom molecular dynamics simulation of tiled six-helical DNAphocholine lipid bilayer where lipid molecules near the DNA nanotubes re106 Copyright 2018 Oxford University Press.18734 | Chem. Sci., 2024, 15, 18715–18750eventually reduced by attaching a cholesterol anchor to DNA.The results of the all-atom molecular dynamics simulationperformed in this study were useful for understanding thephenomenology of DNA nanotubes in lipid bilayers. Thismethodology sets important grounds for lateral nano-architectonics designs at membrane interfaces.In ordinary supramolecular systems, it is challenging tocontrol the long-distance movement of molecules. Cells, on theother hand, utilize molecular motors such as dynein andkinesin and cytoskeletons such as microtubules to move freelyover long distances.107 Inspired by the molecular motors thatenable intracellular transport, lateral nanoarchitectonics aimsto mimic these systems by forming assemblies on membraneinterfaces. Furuta and co-workers designed a protein motor thatmoved alongside DNA nanotubes.108 The motor was fabricatedby combining dynein, a biomolecular motor, with a DNA-binding protein that was responsible for the selective motionon articial DNA tracks with a precisely designed structure. Inaddition to this, the transport of multiple cargoes was presentedby using different motors. This work introduced locallyprogrammable and fully controlled molecular transport. Thefurther development of peptides and other functional polymersand the contribution of lateral nanoarchitectonics will enablehigh-throughput production of new-era nano- and micro-devices, such as external signal receivers, and systems forenergy harvesting and information processing, among others.Basic research on how to immobilize DNA origami on lipidmembranes is crucial for the construction of advanced systems.Self-assembly of nanostructures such as DNA origami onto lipidmembranes is an important element of lateral nano-architectonics. Suzuki and co-workers reported theenvironment-dependent self-assembly of DNA origami latticeson phase-separated lipid membranes.109 In particular, theyinvestigated the environment-dependent assembly of DNAorigami structures on phase-separated lipid bilayers consistingof a liquid disordered phase and a solid ordered phase (Fig. 22).The formation of 2D lattices depended on the uidity of thenanotubes embedded in a 1-palmitoyl 2-oleoyl-sn-glycero-3-phos-orient to form a toroidal structure. Reprinted with permission from ref.© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 22 Environment-dependent self-assembly of DNA origami lattices on phase-separated lipid membranes: DNA origami on the liquiddisordered phase formed 2D lattices, while DNA origami on the solid ordered phase formed aggregates (right AFM image of DNA origami ona lipid membrane). Reprinted with permission from ref. 109 Copyright 2018 Wiley-VCH.Review Chemical Sciencelipids in the bilayer and on the charge density on the bilayersurface. At high charge density, DNA origami formed 2D latticeson the liquid disordered phase due to surface-mediated self-assembly. On the other hand, DNA origami in the solidordered phase formed aggregates because of the lower mobility.There was also a signicant inuence of the ionic strength onthe resulting 2D lattice. The presence of NaCl caused the latticeson the liquid disordered phase to desorb from the surface. Incontrast, the DNA origami aggregates were reorganized intoa lattice on the solid-order phase. In addition, the formation ofthe 2D lattice also depended on the lipid phase. As a result, itwas possible to select the domain in which the lattice wasformed. It was possible to design ra-like domains of DNAorigami that responded to salt/thermal conditions. It can beassumed that combining functional DNA nanostructures bymeans of lateral nanoarchitectonics will lead to the fabricationof articial cells and molecular robots.The morphology of the membrane and its dynamic adapta-tions regulate many cellular functions. Advances in DNAnanotechnology have enabled DNA origami to adopt this role.DNA origami can be an effective tool to articially controlmembrane morphology. Therefore, studying the interaction ofDNA origami with lipid membranes during immobilization isalso an important task in the eld of nanoarchitectonics. Tur-bereld and co-workers examined the modication ofmembrane morphology and interactions with the formation ofDNA origami clathrin mimic networks.110 In particular, theyexamined the assembly of DNA origami meshes on lipidmembranes (Fig. 23). The original DNA triskelia were three-armed DNA origami nanostructures inspired by clathrin,a membrane-modifying protein. DNA origami was bound tolipid monolayers and lipid bilayers using cholesterol anchors;© 2024 The Author(s). Published by the Royal Society of Chemistrypolymerization of the triskelia was triggered by the addition ofDNA staples. As a result, the arms of the triskelia were linked toform a mesh. Large clusters of curved triskelia were formed asa result of polymerization. The unpolymerized DNA triskeliawere uniformly distributed on the surface of the lipid bilayervesicle. The network of polymerized triskelia caused sub-micrometer deformation of the lipid monolayer. This was likethe formation of clathrin-coated pits. The polymerization oftriskelia altered the interactions between the lipid bilayers. Asa result, synapse formation between the giant unilamellarvesicles and the supporting lipid bilayer was inhibited. Thisstudy shows that the lateral nanoarchitectonics of DNA origamistructures on the membrane surface provides a tool to controlthe dynamic behaviour of lipid membranes, their shape, andinteractions. This will be useful for the development of biomi-metic systems for signal transduction, synthesis, and repro-duction based on membrane-bound compartments.The control of lipid membrane morphology by dynamic DNAorigami networks was reported by Yang et al. (Fig. 24).111 In thisstudy, DNA origami cross-structures were anchored to giantunilamellar vesicles. The adsorbed DNA origami crosses werepolymerized into micrometer-scaled 1D chains or 2D lattices.The cross-chiral structure, which could be both polymerizedand reconstituted, was demonstrated. Through this, themembrane morphology of the giant unilamellar vesicles wasdesigned; polymerization aer anchoring the DNA origamicrosses to the giant unilamellar vesicles deformed themembrane depending on the degree of polymerization. Toconclude, mimicking membrane deformation with program-mable dynamic DNA nanostructures can mimic fundamentalcellular processes such as endocytosis and exocytosis. Whenthese ndings are adopted, it is possible to develop DNAChem. Sci., 2024, 15, 18715–18750 | 18735Fig. 23 (Top) DNA triskelia in three-armed DNA origami nanostructures for dimers and different conformations; (bottom) polymerization of thetriskelia on a lipid bilayer membrane to assemble into mesoscopic domains. Reproduced under terms of the CC-BY license from ref. 110, 2019American Chemical Society.Chemical Science Reviewnanomachines that generate contractile forces and manipulatethe morphology of living cells.6.2. Articial signal transductionCell membranes play a key role in signal transduction andphotosynthesis. To perform such complex tasks, functionalmolecules, such as pigments and proteins, are rationallyarranged within the cell membrane to perform highly efficientfunctions. Naturally, there have been several attempts to mimicsimilar systems. As shown below, an articial receptor and anenzyme (lactate dehydrogenase, LDH) worked in tandem ona lipid bilayer to assemble an articial signal transductionsystem.112 In this bilayer device, the articial receptor wasdesigned to initiate the enzymatic reaction aer detecting anexternal chemical input signal (Fig. 25A). Here, LDH was immo-bilized in the lipid membrane with steroidal amines as effectorsand receptors; the role of G proteins in the natural signal trans-duction system is carried out by copper ions, which are inhibitorsof the enzyme. The mechanism of action was described asfollows. First, the enzyme was inhibited (OFF state) in the pres-ence of copper ions. When an aldehyde substance was introducedto the system, it bound to the articial receptor upon theformation of a Schiff base that captured the copper ion inhibitors.With the inhibitor removed, the enzyme became active (ON state).As a system in which the two signals are logically linked, anazobenzene-type receptor was used (Fig. 25B).113 When the18736 | Chem. Sci., 2024, 15, 18715–18750azobenzene moiety was in the cis form, the recognition siteswere not properly associated and the ability to capture copperions was reduced. When the azobenzene moiety was in the transconguration, the coordination ability of the copper ion wasconformationally higher. Differences in enzyme activity wereobserved in systems containing trans- and cis-type receptors. Ata concentration of 4 mM copper ions, the enzyme activity was53% in the system containing the trans-type receptor, while itwas only approximately 6% in the system with the cis-typereceptor. The azobenzene-type receptor showed the same sig-nalling behaviour as the steroidal-type receptor, meaning thatexposure of LDH to copper ions for a long period caused certainirreversible changes and a decrease in LDH activity over time.Devices with the ability to repeatedly turn the activity of LDH onand off could be manufactured if appropriate conditions arechosen. The presented system can be thought of as a switchingdevice with optical signals. It can also be thought of as a logicdevice in which two types of signals, chemical and optical,represent an input. The presence of a signalling molecule isconsidered true (absence is false), and irradiation with visiblelight is considered true (irradiation with ultraviolet light isfalse). In this system, the output, maintenance of enzymeactivity, is obtained only when both the chemical and opticalsignals are true. Therefore, this system can be regarded as anAND-type logic circuit. Since this system can freely exchangeand combine enzymes and receptors, it is expected that other© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 24 DNA origami cross structures anchored to giant unilamellar vesicles; polymerization of the DNA origami crosses deforms themembraneto different degrees depending on the degree of polymerization. Reprinted with permission from ref. 111 Copyright 2023 American ChemicalSociety.Review Chemical Sciencetypes of logic circuits can also be developed. By combiningseveral types of logic circuits, a nanothin-lm calculator capableof simple arithmetic operations may be fabricated.This can be achieved by using lipid bilayers as a medium toarrange functional components in lateral nanoarchitectonics toachieve functional linkage. Depending on the combination,switching and logic devices can be constructed. This concepthas the potential to be deployed in a wide variety of ways.6.3. Conjugated biomolecular machinesSimilarly, there is also research on nanoarchitectonics ofbiomolecular machines and articial structures on nanolmsprepared by lipid bilayer vesicles or LbL assembly to achieveinterlocking functions. The research group led by Li and co-workers has made signicant advances in this eld.114 Someof the results are listed below.Insight into biological pathways is crucial for designing andconstructing organelle-like and cell-like structures. Lateralnanoarchitectonics represents a branch of the convergence ofmaterials science and biodesign, enabling the construction ofcomplex systems that mimic and enhance natural processes.Specically, signicant efforts have been made to improveenergy conversion efficiency within biomimetic systems.Adenosine triphosphate (ATP), the primary energy currency ofliving organisms, plays an important role in the regulation ofenergy-dependent metabolic processes such as proteinsynthesis, signal transduction, and mass transport. Naturally,© 2024 The Author(s). Published by the Royal Society of ChemistryATP is predominantly produced by ATP synthase in mitochon-dria, chloroplasts, and bacterial cytoplasmic membranes,driven by a transmembrane proton gradient. Lateral nano-architectonics for mimicking and modifying transmembrane-based subcellular functional units offers innovativeapproaches for bioenergy conversion.A breakthrough developed by Li et al. involved improvingATP generation by constructing microcapsules with orientedbacteriorhodopsin (BR) using the LbL assembly technique(Fig. 26A).115 MnCO3 microspheres as removable templates, andpolyetherimide (PEI), BR, poly(sodium-p-styrenesulfonate)(PSS), and poly(allylamine hydrochloride) (PAH) were succes-sively adsorbed on the surface of the MnCO3 microspheres byLbL assembly. BR presented an oriented structure in the LbLassembly. To fabricate the microcapsules, the MnCO3 core wasremoved using ethylenediaminetetraacetic acid disodium salt(EDTA-Na2). The hollow microcapsules were then coated withFoF1-ATPase molecular motors. Oriented BR facilitated direc-tional proton migration under illumination, thereby increasingthe proton gradient necessary for ATP synthesis.Another notable development involved the use of semi-conducting graphitic carbon nitride (g-C3N4) nanosheetsapplied as a photozyme within microcapsules, co-assembledusing the LbL deposition method with polyelectrolytes tomimic mitochondria (Fig. 26B).116 This system showedenhanced separation of photogenerated electron–hole pairs,accelerating the oxidation of glucose into gluconic acid andChem. Sci., 2024, 15, 18715–18750 | 18737Fig. 25 Artificial signal transduction with receptor molecules and lactate dehydrogenase (LDH) on lipid membranes: (A) chemical signal controland (B) photo signal control.Chemical Science Reviewgenerating protons under light. These protons established anoutward transmembrane proton gradient, which drove ATPsynthase to synthesize ATP. This articially designed assemblyexhibited higher energy conversion efficiency than conventionaloxidative phosphorylation systems, offering a novel method forchemical-to-biological energy conversion.To further enhance photosynthetic efficiency, Li and co-workers co-assembled natural thylakoid membranes (TM)with articial long aerglow particles (LAPs) (Fig. 26C).117 TheLAP is known for its light conversion and storage capabilities. Inthis work, the LAP was optically matched with the absorptionspectrum of TM. This assembly facilitated enhanced photo-synthesis, as evidenced by increased rates of electron transfer,oxygen yield, and ATP production. Notably, the persistentphosphorescence emission from charged LAPs enabledcontinued photosynthesis in the dark, signicantly improvingnatural systems that terminate photosynthesis immediatelyupon the onset of darkness.18738 | Chem. Sci., 2024, 15, 18715–18750The innovative approach of this group to ATP synthesis alsoincluded the use of boric acid as a new fuel source within an LbLassembly-related microcapsule (Fig. 26D).118 In this study,protons sequestered in boric acid were modulated and releasedby polyols. This controlled release of protons establisheda proton gradient across a lipid membrane, effectively drivingthe embedded ATP synthase to synthesize ATP from ADP andinorganic phosphate (Pi). This research introduced a novelmethod for bioenergy conversion and highlighted the potentialof nonredox processes in articial bioenergy production.Lastly, to mimic the mitochondrial bioenergy anabolism,a nanoarchitecture was designed with a dendritic mesoporoussilica microparticle (DMSM) as the inner compartment, whichloaded NADH as the proton source and enabled rapid masstransfer (Fig. 26E).119 The outer compartment consisted ofproteoliposomes reconstituted with ATP synthase. A syntheticelectron shuttle, tetracyanoquinodimethane (TCNQ),embedded in the lipid bilayer, mediated transmembrane redox© 2024 The Author(s). Published by the Royal Society of ChemistryFig. 26 Schematics of various artificial bioenergy conversion systems. (A) LBL assembly of microcapsules using MnCO3 microspheres asremovable templates and supporting FoF1-ATPase proteoliposomes. The enlarged view shows how oriented BR pumps protons integrated intothe microcapsules, driving FoF1-ATPase to synthesize ATP from adenosine diphosphate (ADP) and inorganic phosphate (Pi) under light irradi-ation. (B) The ATP synthase-reconstituted architecture for light-driven oxidative phosphorylation. Under light irradiation, g-C3N4-PEI on themicrocapsule shell acts as a photozyme, catalyzing glucose transformation into gluconic acid with oxygen, creating a proton gradient for ATPsynthesis. (C) Biohybrid architecture integrating spectral and temporal light management. Based on the luminescence mechanism, under lightirradiation, long afterglow particles (LAPs) can convert harmful UV light to visible light, enhancing the photosynthetic activity of natural thylakoidmembranes (TM). In the dark, the long-life phosphorescence of LAPs can continue to drive photophosphorylation by TM. FL: fluorescenceluminescence; PL: phosphorescence luminescence; ETC: electron transport chain. (D) An artificial bioenergy conversion system based onpolyelectrolyte microcapsules supports ATP synthase-containing liposomes. In the presence of polyols, protons locked in boric acid arereleased, generating a proton gradient that drives ATP synthase to convert ADP and Pi into ATP. (E) An electron shuttle in an ATP synthase-reconstituted nanoarchitecture for enhanced bioenergy anabolism, inspired by natural mitochondria. The cross-section shows the bio-likesystem and transmembrane chemical reactions. Driven by tetracyanoquinodimethane (TCNQ) as the electron shuttle in the lipid bilayer,electrons flow from NADH to [Fe(CN)6]3. DMSM: dendritic mesoporous silica microparticle. Reprinted with permission from ref. 115 Copyright2022 Wiley-VCH, ref. 116 Copyright 2023 American Chemical Society, ref. 117 Copyright 2023 Elsevier, ref. 118 Copyright 2021 Wiley-VCH, andref. 119 Copyright 2024 Wiley-VCH.© 2024 The Author(s). Published by the Royal Society of Chemistry Chem. Sci., 2024, 15, 18715–18750 | 18739Review Chemical ScienceChemical Science Reviewreactions, converting NADH to NAD+ and generating a protongradient. This gradient led ATP synthase to rotate and synthe-size ATP efficiently and sustainably, opening new avenues forenhanced bioenergy anabolism in a wide range of ATP-poweredbioapplications.6.4. Aqueous organic semiconductor lmsThe numerous examples in the previous sections have shownthat nanoarchitectonics at the membrane interface in water isa useful approach to mimic biological functions and buildadvanced functional systems. Not only such biosystems, butnanoarchitectonics at the aqueous solution interface are alsouseful in a wide range of scientic and engineering elds.Finally, we discuss the importance of lateral nanoarchitectonicsat the membrane interface using an example from a completelydifferent eld. This section will briey introduce doping nano-architectonics for organic semiconductor thin lms inconjunction with chemical equilibria at the aqueous interfaces.Chemical doping using reactions with redox reagents wasused to dope organic semiconductors. However, redox reagentsare prone to degradation in the presence of water and/or air, andtheir use is restricted to environments of inert gases and vacuum.In addition, it is not easy to introduce dopant molecules withoutdisturbing the crystal structure of organic semiconductors,which are formed only by weak intermolecular forces. Dopingthat meets all these challenges is not easy. Ishii, Yamashita andco-workers solved all these problems by molecularly dopingnanoarchitectonics at the interface between aqueous solutionand the thin lm of organic semiconductors (Fig. 27).120 Theinspiration came from coupling with the biochemical reaction,Fig. 27 Doping of organic semiconductors attempted in an aqueous soelectron transfer reactions. Reprinted with permission from ref. 120 Cop18740 | Chem. Sci., 2024, 15, 18715–18750which takes place in water, i.e. proton-coupled electron transfer.It is a reaction in which positively charged protons and negativelycharged electrons move in synchronisation with each other. Itsequilibrium depends on the concentration of protons, alsoexpressed as pH. Using this method, the redox reaction thatoccurs in water can be precisely controlled by using the pH of theaqueous solution. Doping of organic semiconductors wasattempted in an aqueous solution using benzoquinone andhydroquinone as proton-conjugated electron transfer reactions.Thin lms of organic semiconductors were immersed in aqueoussolutions of benzoquinone, hydroquinone, and bis(tri-uoromethylsulfonyl)imide anion (TFSI−). The TFSI− repre-sented an anion that plays the role of a dopant in p-typesemiconductors. The benzoquinone used in this study was con-verted to hydroquinone without producing an anion molecule inthe process. Therefore, the hydrophobic anion TFSI− was addi-tionally dissolved in the dopant solution. When benzoquinonewas oxidized a hole was formed in the organic semiconductorlm, enabling the incorporation of the TFSI− dopant. This divi-sion of tasks enabled the use of proton-conjugated electron-transfer-type redox reagents such as benzoquinone/hydroquinone for chemical doping. A notable advantage ofusing benzoquinone/hydroquinone solutions is their excellentreproducibility and pH-dependent controllability. By adjustingthe pH of the aqueous solution, the electrical conductivity of theorganic semiconductors was controlled with high precision. Thisdoping nanoarchitectonics is an extremely simple process thatinvolves only immersion of a thin lm of organic semi-conductors in an aqueous solution. When the process is per-formed in water, the method is able to overcome the traditionalproblems of organic semiconductor doping. These processes arelution using benzoquinone and hydroquinone as proton-conjugatedyright 2023 Springer-Nature.© 2024 The Author(s). Published by the Royal Society of ChemistryReview Chemical Sciencebased on coupling of chemical equilibrium and membranelateral electrical conductions at the interface. The construction ofmembrane systems by lateral nanoarchitectonics on such dopingsystems would create circuit-like two-dimensional architectures.In several of the previous sections, we have presented diverseexamples of lateral nanoarchitectonics at membrane interfacesin contact with aqueous solutions. Operating in aqueous solu-tion systems and using lipid bilayer structures as interfacialmedia, a wide variety of biomaterials can be assembled forfunctionality; elements that can be highly programmable instructure can be incorporated, such as DNA origami, enzymes,and biomolecular motors. It was also demonstrated that ndinginspiration in biological equilibrium reactions allows forprecise doping nanoarchitectonics of organic semiconductors.In lateral nanoarchitectonics at the aqueous interface,advanced biological phenomena and semiconductor engi-neering can be coupled. This suggests a promising eld for thedevelopment of new innovative functions, such as wet devices.7. Living cells at the liquid–liquidinterfaceMany of the previous examples have focused on functionalcoordination in various types of cellular membranes. Cellularmembranes comprise highly organized molecules that alloweffective signal transmission to the interior of the cell and directvarious complex biological functions. The plasma membrane,as well as other organelle membranes, is therefore an idealplatform for developing lateral nanoarchitectonics. However,lateral nanoarchitectonics is not limited to mimicking andmodifying the plasma membrane or organelle membranes totransport signals or enhance biological energy conversion. Itcan also be a crucial approach for the construction of theextracellular matrix (ECM) and the ne-tuning of the regulationof cellular fate. To fully understand the potential applications oflateral nanoarchitectonics, it is important to examine how cellsinteract with articial interfaces. Although there is extensiveresearch on cell behaviour on solid surfaces,121 the study of cellbehaviour at liquid–liquid interfaces—independent of solidenvironments—is still in the early stages.122Some notable advancements in this area are highlighted inthe following section. For example, Jia and colleagues havepresented signicantly advanced lateral nanoarchitectonics forECM connement in cell culture, based on peruorocarbon–water interfacial systems. This research underscores theimportance of exploring how mechanical cues in cellularmicroenvironments inuence key cell functions, such asspreading and differentiation.Traditionally, studies used solid substrates, assuming cellscannot spread on uid substrates due to rapid relaxation, whichfails to resist actomyosin-based cell contractility. However, Jiaet al. demonstrated that anchorage-dependent cells, includinghuman mesenchymal stem cells (hMSCs), can spread and growat the liquid interface between a peruorocarbon uid and theculture medium (Fig. 28A).123 This phenomenon was facilitatedby the self-assembly of a monomolecular protein nanosheet at© 2024 The Author(s). Published by the Royal Society of Chemistrythe uid interface, which provided sufficient rigidity to supportcell spreading without additional treatment. The stiffness of theprotein monolayer was regulated by ne-tuning the packing ofproteins at the liquid interface. The increased stiffness of theprotein nanosheets triggered cell spread, adhesion growth, andnuclear translocation of the yes-associated protein (YAP). Thisbehaviour aligned with the molecular clutch model, offeringinsights into how cells interact with such adaptive uid envi-ronments. Furthermore, these freestanding ultrathin proteinnanosheets were extremely exible, easily deformed, andperceived by cells as much soer than solid substrates,providing new perspectives on cell–material interactions.The dynamic nature of the native ECM involves continuousfeedback between cells, which plays a crucial role in regulatingcell functions. A lysozyme molecule lacks specic integrin-binding motifs; however, lysozyme-assembled nanosheetspresent naturally positively charged surfaces that facilitate cellattachment and the subsequent spread of cells. Lyu et al. builtan adaptive environment based on self-assembled lysozymemonolayers at the FC40 peruorocarbon–water interface thatattempted to mimic the dynamic nature of the ECM(Fig. 28B).124 The dynamic adaptivity of interfacial assembledprotein nanosheets was modulated independent of bulkmechanical properties through covalent crosslinking, allowingbidirectional interactions between cells and liquid interfaces ofvarying dynamic adaptivity. This approach enhanced thegrowth and multipotency of hMSCs, mediated by low cellcontractility and metabolic activity, involving continuousmutual feedback between cells and materials.Adaptive materials composed of a protein monolayerassembled at a liquid–liquid interface dynamically adapt to celltraction forces. Jia et al. investigated detailed cell–materialinteractions by establishing a bronectin-enriched proteinmonolayer at the peruorocarbon–water interface for stem cellculture. Through interfacial jamming, an ultrastructure transi-tion from a protein monolayer to hierarchical bers was re-ported to promote the kinase activation and neuronaldifferentiation of stem cells (Fig. 28C).125 Cell traction forcesresulted in the spatial rearrangement of ECM proteins, whichreacted to alter the stem cell fate. This biomimetic adaptiveliquid interface enabled dynamic control of stem cell behaviour,with signicant translational potential.It is understood that the fates of stem cells are cooperativelydriven by their microenvironment interactions. Biomaterialsare dynamically remodelled by stem cells, which sense andtranslate these changes into cell fate decisions. Previously re-ported adaptive biomaterials composed of bronectin insertedinto protein nanosheets at a liquid interface enhanced neuronaldifferentiation of hMSCs. However, distinguishing the effects ofligand density from those of brillary structure on cellularfunction and fate was challenging. Jia et al. constructed a noveladaptive biomaterial using 2D networks of protein nanobrilsassembled at a liquid–liquid interface (Fig. 28D).126 Comparedto at protein nanosheets, 2D hierarchical nanosheets based onprotein nanobrils improved the neuronal differentiation ofhMSCs through a focal adhesion kinase signalling mechanism.The lipid ra microdomains in the plasma membrane playedChem. Sci., 2024, 15, 18715–18750 | 18741Fig. 28 Liquid–liquid interfacial assembled 2D protein monolayer nanosheet based culture system for hMSC fate controlling. (A) A photographand illustrations present the formation of a protein monolayer at the liquid–liquid interface, resulting from the denaturation and self-assembly ofserum proteins. The response of hMSCs to the stiffness of the protein monolayer is clarified through the actin–integrin–fibronectin (FN) clutchmechanism. (B) Lysozyme monolayers, self-assembled at the liquid interface, are shown to maintain the self-renewal and multipotency ofhMSCs. The lysozyme forms a close-packed monolayer through hydrophobic interactions among b-sheet-rich oligomers. Enhancing theretention of multipotency by reducing cytoskeletal tension and glycolysis activity was verified. The figure also labels key glycolytic intermediates:fructose 6-phosphate (F6P) and fructose 1,6-bisphosphate (F1,6BP). (C) The adaptive self-assembled protein monolayer is responsive to thetraction forces produced by cells, which in turn guides the differentiation of hMSCs. (D) The figure illustrates the neuronal differentiation ofhMSCs at the interface, where a 2D network of protein nanofibrils is assembled. This differentiation process is related to lipid raft assembly andthe phosphorylation of focal adhesion kinase (FAK). Reprinted with permission from ref. 123 Copyright 2019 Wiley-VCH, ref. 124 Copyright 2023Wiley-VCH, and ref. 125 Copyright 2019 Wiley-VCH. Reproduced under terms of the CC-BY license from ref. 126, 2022 Springer-Nature.Chemical Science Reviewa central role in how the hMSCs rapidly adapted to the dynamicmicroenvironment at the uid interface. These ndings havesubstantial implications for regenerative medicine and tissueengineering, highlighting the importance of individualized andprecise design adaptive biomaterials in controlling cell behaviorand fate.Inspired by adaptive mechanisms found in natural systems,lateral nanoarchitectonics has paved the way for the creation of18742 | Chem. Sci., 2024, 15, 18715–18750recongurable all-liquid structures, offering a unique approachto material design. These systems, where living cells areanchored at liquid–liquid interfaces, provide a so, exible, anddynamic platform that adapts to mechanical forces generatedby the cells themselves. This dynamic environment, whichclosely mimics the natural extracellular matrix, supports cellgrowth, signal transmission, and various complex biologicalfunctions in real time.© 2024 The Author(s). Published by the Royal Society of ChemistryReview Chemical ScienceOne of the most promising applications of this technology isin the eld of stem cell research. Stem cells, due to their mul-tipotency, can differentiate into various cell types, includingbone, cartilage, and neural cells. By utilizing lateral nano-architectonics at liquid–liquid interfaces, a controlled environ-ment is created to ne-tune the biochemical and biophysicalcues necessary for directing stem cell fate. For example, soer,more elastic surfaces may favor neural cell development, whilebioactive molecules introduced at the interface can enhanceprecision, creating highly specialized cellular environmentstailored for tissue-specic engineering.The ability to control stem cell behavior in this way isparticularly signicant for regenerative medicine, where precisedifferentiation is crucial for replacing damaged tissues withfunctional ones. Platforms designed using lateral nano-architectonics at the peruorocarbon–water interface not onlysupport cell growth but also guide it in a highly controlledmanner, opening up new possibilities for creating tissues thatclosely resemble their natural counterparts in both structureand function. This could greatly improve treatments forconditions such as bone fractures, cartilage damage, andneurodegenerative diseases.Overall, lateral nanoarchitectonics holds great potential foradvancing biomedical science by leveraging the unique prop-erties of liquid–liquid interfaces and integrating functionalnanoscale materials. This approach positions nano-architectonics as a key technology in the development of next-generation medical treatments, where biomaterials interactwith cells in adaptive and responsive ways.8. Summary and perspectivesIn this review paper, under the theme of lateral nano-architectonics, we have examined the rational extension offunctional structures within a single plane: their organization,interlocking of functional units, and the exploration of thepotential for the expression of advanced bioinspired functions.Overall trends have been explored, encompassing a wide varietyof examples that range from the creation of structures at themolecular level to the regulation of cell differentiation. In manysystems, we found that, while the targets are very attractive, theresearch is in its infancy, and many challenges remain to beovercome.Molecular lateral nanoarchitectonics is in its early stages ofresearch in terms of structural complexity and function. Theextension of molecular structures by on-surface synthesis is inits infancy, but is conceptually highly innovative. These effortsbreak the rules of organic synthesis and change the history oforganic chemistry. The organic synthesis pathway of on-surfacesynthesis is not based on probabilistic collisions or energystability in solution. Conventional molecular synthesis islimited by the rules of organic chemistry. Lateral nano-architectonics has the potential to develop completely newtrends in organic chemistry by inserting targeted functionalgroups into targeted sites on a plane. Although some workneeds to be done in terms of productivity, the use of lateralnanoarchitectonics in nano-level devices may lead to© 2024 The Author(s). Published by the Royal Society of Chemistrya revolutionary development. The interlocking of moleculargears also provides an example of something that is imagina-tively possible, but difficult to realize in practice. However, oncethe fundamentals of molecular machine manipulation areestablished at a given position on a surface, the stage ofbuilding it will proceed quickly. Such an example was achievedin surface-operated systems with DNA origami. Supramolecularcoordination of molecular machines on surfacesmay lead to theconstruction of smaller, more precise, but intricately inter-locking machines on surfaces.Many lateral nanoarchitectonics systems that incorporatebiofunctional molecules are functionally advanced. It is mean-ingful to organize molecular motors, enzymes, and other mole-cules that themselves exhibit high functionality on membranesin terms of functional coordination. Although actual functionalcoordination has been achieved, there are few examples ofadvanced functional systems in which many functional elementswork in tandem. More efforts should be made to articiallycreate functional systems such as those found in cells in whicha number of functional systems work in tandem upon stimula-tion from the interface. Lipid membrane ra models and DNAorigami on lipid membranes can be used as tools for thispurpose. Although not mentioned in this review, peptideassembly structures have also been used to reproduce advancedbiological functions. Programmed peptide assembly structures127as well as much advanced DNA nanotechnologies may also beuseful for such functional organization. It is hoped that moreadvanced functional systems containing biological functions willbe constructed by lateral nanoarchitectonics using these tools.Lateral nanoarchitectonics, in which more complex recog-nition sites are formed by the assembly of simple molecules ina single molecular plane at the water surface, is a pioneeringconcept. However, this eld does not seem to be developingrapidly. New developments seem to require integration with thesynthesis of MOFs and COFs at interfaces and progress in thesynthesis of supramolecular polymers and gel bers. Thesetechnologies are oen based on single or simple components.With the development of techniques such as multicomponentstructure formation and stepwise structure evolution, morecomplex structures can be designed in the lateral directionwithin the secondary exemptions. In such a case, if a systemsuch as receptor creation by molecular assembly is incorpo-rated, it will be possible to construct a kind of cascade system inwhich multiple functions are interlocked, or a 2D energy-intensive functional system. Lateral nanoarchitectonics, suchas 2D dendrimer-like MOFs, COFs, and supramolecular poly-mers, may be required. As a dynamic linkage element, the use ofmicro-robots that run on their own at the interface is alsoattractive. The creation of bio-/articial devices by linking suchinterlocking functions with organic semiconductor thin lmsalso represents a futuristic challenge.A specic and unique system in nanoarchitectonics at theinterface is the coupling of macro- and nanoscale phenomena.Molecular machines arranged at the interface can be subjectedto macroscopic mechanical stimuli from the lateral direction ofthe membrane. The collective motion of molecular rotors at theliquid interface can also be detected as macroscopic signals.Chem. Sci., 2024, 15, 18715–18750 | 18743Chemical Science ReviewThis is because the liquid interface can link the macroscopicmotion in the lateral direction with the molecular motion onthe membrane surface. So far, such an idea has only been usedfor simple molecular machine systems, and when moresophisticated functional coordination systems are constructedin the interfacial membrane by lateral nanoarchitectonics, theywill be controllable by macroscopic motion. Macroscopicmotion is compatible with the movements of human daily life.Therefore, if such a 2D complex system is constructed, it will bepossible to control advanced functional systems with humandaily movements.Of course, all the possible candidates in lateral nano-architectonics cannot be mentioned in one review article. Wehave to note that there are many other possibilities. Tocomplement this molecular machine's intricate mechanicaldesign, Dip-Pen Nanolithography (DPN) offers an alternativemethod for molecular manipulation, focusing not on inter-locking motions but on precise molecular deposition andsurface patterning.128 This lateral organization of molecules onsurfaces is a core aspect of lateral nanoarchitectonics, enablingthe construction of nanoscale devices where surface interac-tions and patterning are critical. By precisely controllingmolecular deposition, DPN allows for the development of highlyspecialized materials and structures, offering new possibilitiesin areas such as molecular electronics, biosensing, and nano-fabrication. Similar emphasis has to given to the other powerfulcandidates. Supported bilayer membranes129 denitely haveimportant contributions to lateral nanoarchitectonics.However, there is a danger of falling into a too diverse andindividualistic discussion. Therefore, a data-driven approach isimportant rather than relying on the experience and knowledgeof researchers. It is worth noting that articial intelligence ismaking remarkable progress and machine learning enablesoptimization and direct research in a data-driven manner.130 Infact, in the development of nanoporous materials, the necessityof integrating material informatics and nanoarchitectonics hasbeen discussed.131 The development of functional systems bylateral nanoarchitectonics will also be advanced to morecomplex and sophisticated systems by the introduction of arti-cial intelligence.Data availabilityNo primary research results, soware or code have beenincluded and no new data were generated or analysed as part ofthis review.Author contributionsJ. S.: conceptualization, writing, review & editing. A. J.-P.:conceptualization, writing & editing. K. K.: project administra-tion, review & editing. K. A.: conceptualization, writing, review &editing, funding acquisition.Conflicts of interestThere are no conicts to declare.18744 | Chem. Sci., 2024, 15, 18715–18750AcknowledgementsThis study was partially supported by the Japan Society for thePromotion of Science KAKENHI (Grant Numbers JP20H00392,JP23H05459 and JP24KF0086).Notes and references1 (a) K. Maeda, F. Takeiri, G. Kobayashi, S. Matsuishi,H. Ogino, S. Ida, T. Mori, Y. Uchimoto, S. Tanabe,T. Hasegawa, N. Imanaka and H. Kageyama, Bull. Chem.Soc. Jpn., 2022, 95, 26–37; (b) M. Kim, K. L. Firestein,J. F. S. Fernando, X. Xu, H. Lim, D. V. Golberg, J. Na,J. Kim, H. Nara, J. Tang and Y. Yamauchi, Chem. Sci.,2022, 13, 10836–10845; (c) T. Meng, Z. Li, L. Wang, K. Shi,X. Bu, S. M Alshehri, Y. Bando, Y. Yamauchi, D. Li andX. Xu, Bull. Chem. Soc. Jpn., 2023, 96, 907–912; (d) T. Du,Z. Chen, F. Dong, H. Cai, Y. Zou, Y. Zhang, P. Sun andM. Xu, Adv. Funct. Mater., 2024, 34, 2313794; (e) J.-C. Feng,N. Wei, Z. Sun, S.-X. Li, X. Li and H. Xia, Nano Energy,2024, 123, 109409.2 (a) Y. Shan, G. Zhang, W. Yin, H. Pang and Q. Xu, Bull.Chem. Soc. Jpn., 2022, 95, 230–260; (b) A. R. Kottaichamy,S. Deebansok, J. Deng, M. A. Nazrulla, Y. Zhu, Z. M. Bhat,M. C. Devendrachari, C. P. Vinod, H. M. Kotresh,O. Fontaine and M. O. Thotiyl, Chem. Sci., 2023, 14, 6383–6392; (c) T. Fukushima, M. Higashi and M. Yamauchi,Bull. Chem. Soc. Jpn., 2023, 96, 1209–1215; (d)N. I. Ibrahim, A. Yahiaoui, J. A. Garkuwa, R. B. Mansourand S. Rehman, J. Energy Storage, 2024, 97, 112762.3 (a) C. E. Housecro and E. C. Constable, Chem. Sci., 2022,13, 1225–1262; (b) Y. Tsuchii, T. Menda, S. Hwang andT. Yasuda, Bull. Chem. Soc. Jpn., 2023, 96, 90–94; (c)Y. Liang, C. Jiao, P. Zhou, W. Li, Y. Zang, Y. Liu, G. Yang,L. Liu, J. Cheng, G. Liang, J. Wang, Z. Zhong and W. Yan,Bull. Chem. Soc. Jpn., 2023, 96, 148–155; (d) Z. Zhang,W. Wang, H. Rao, Z. Pan and X. Zhong, Chem. Sci., 2024,15, 5482–5495; (e) A. Phengdaam, S. Phetsang, S. Jonai,K. Shinbo, K. Kato and A. Baba, Nanoscale Adv., 2024, 6,3494–3512.4 (a) D. Guo, R. Shibuya, C. Akiba, S. Saji, T. Kondo andJ. Nakamura, Science, 2016, 351, 361–365; (b) Y. Takeuchi,K. Matsuzawa, T. Nagai, K. Ikegami, Y. Kuroda,R. Monden and A. Ishihara, Bull. Chem. Soc. Jpn., 2023,96, 175–177; (c) X. Wang, S. Wu, R. Yang, H. Song, Y. Liuand Q. Wang, Chem. Sci., 2023, 14, 13367–13383; (d)J. Yano, K. Suzuki, C. Hashimoto, C. Tsutsumi, N. Hayaseand A. Kitani, Bull. Chem. Soc. Jpn., 2023, 96, 331–338; (e)S. Li, L. Shi, Y. Guo, J. Wang, D. Liu and S. Zhao, Chem.Sci., 2024, 15, 11188–11228; (f) G. Chen, M. Isegawa,T. Koide, Y. Yoshida, K. Harano, K. Hayashida, S. Fujita,K. Takeyasu, K. Ariga and J. Nakamura, Angew. Chem., Int.Ed., 2024, e202410747.5 (a) T. Hosaka and S. Komaba, Bull. Chem. Soc. Jpn., 2022, 95,569–581; (b) B. Tao, D. Zhong, H. Li, G. Wang and H. Chang,Chem. Sci., 2023, 14, 8693–8722; (c) P. Ganesan, A. Ishihara,© 2024 The Author(s). Published by the Royal Society of ChemistryReview Chemical ScienceA. Staykov and N. Nakashima, Bull. Chem. Soc. Jpn., 2023,96, 429–443; (d) A. Yamada, Adv. Sci., 2024, 11, 2401739.6 (a) Md. S. Islam, Y. Shudo and S. Hayami, Bull. Chem. Soc.Jpn., 2022, 95, 1–25; (b) P. A. Shinde, Q. Abbas,N. R. Chodankar, K. Ariga, M. A. Abdelkareem andA. G. Olabi, J. Energy Chem., 2023, 79, 611–638; (c)G. Zhang, Q. Bai, X. Wang, C. Li, H. Uyama and Y. Shen,Bull. Chem. Soc. Jpn., 2023, 96, 190–197; (d) P. A. Shinde,N. R. Chodankar, H.-J. Kim, M. A. Abdelkareem,A. A. Ghaferi, Y.-K. Han, A. G. Olabi and K. Ariga, ACSEnergy Lett., 2023, 8, 4474–4487; (e) R. Gupta, A. Malik,K. Kumari, S. K. Singh, V. Vivier and P. C. Mondal, Chem.Sci., 2024, 15, 8775–8785.7 (a) G. Chen, F. Sciortino and K. Ariga, Adv. Mater. Interfaces,2021, 8, 2001395; (b) T. Ema, Bull. Chem. Soc. Jpn., 2023, 96,693–701; (c) H. Fujimoto, K. Yasui and M. Tobisu, Bull.Chem. Soc. Jpn., 2023, 96, 872–886; (d) T. Tang, X. Bai,Z. Wang and J. Guan, Chem. Sci., 2024, 15, 5082–5112; (e)J. Yang, Z. Yang, J. Li, H. Gang, D. Mei, D. Yin, R. Deng,Y. Zhu, X. Li, N. Wang, S. M. Osman and Y. Yamauchi,Mater. Horiz., 2024, 11, 2032–2040.8 (a) E. Zhang, Q. Zhu, J. Huang, J. Liu, G. Tan, C. Sun, T. Li,S. Liu, Y. Li, H. Wang, X. Wan, Z. Wen, F. Fan, J. Zhang andK. Ariga, Appl. Catal., B, 2021, 293, 120213; (b) M. Xiao,Z. Wang, K. Maeda, G. Liu and L. Wang, Chem. Sci., 2023,14, 3415–3427; (c) J. Wang, X. Li, T. Zhang, X. Chai,M. Xu, M. Feng, C. Cai, Z. Chen, X. Qian and Y. Zhao,Chem. Sci., 2024, 15, 7596–7602; (d) T. Higashi andK. Domen, ChemSusChem, 2024, e202400663; (e)T. Takayama, A. Iwase and A. Kudo, ACS Appl. Mater.Interfaces, 2024, 16, 36423–36432.9 (a) A. Muranaka, H. Ban, M. Naito, S. Miyagawa, M. Ueda,S. Yamamoto, M. Harada, H. Takaya, M. Kimura,N. Kobayashi, M. Uchiyama and Y. Tokunaga, Bull. Chem.Soc. Jpn., 2022, 95, 1428–1437; (b) L. F. Yang, M. Ling,N. Kacherovskya and S. H. Pun, Chem. Sci., 2023, 14,4961–4978; (c) T. Murata, K. Minami, T. Yamazaki,T. Sato, H. Koinuma, K. Ariga and N. Matsuki, Bull. Chem.Soc. Jpn., 2023, 96, 29–34; (d) S. d. K. Sundaram,Md. M. Hossain, M. Rezki, K. Ariga and S. Tsujimura,Biosensors, 2023, 13, 1018; (e) M. Nagao, T. Masuda,M. Takai and Y. Miura, J. Mater. Chem. B, 2024, 12, 1782–1787.10 (a) M. Matsuya, H. Sasabe, S. Sumikoshi, K. Hoshi,K. Nakao, K. Kumada, R. Sugiyama, R. Sato and J. Kido,Bull. Chem. Soc. Jpn., 2023, 96, 183–189; (b) M. Liu,G. Salinas, J. Yu, A. Cornet, H. Li, A. Kuhn and N. Sojic,Chem. Sci., 2023, 14, 10664–10670; (c) Y. Yamamoto,H. Yano, S. Karashima, R. Uenishi, N. Orimo, J. Nishitaniand T. Suzuki, Bull. Chem. Soc. Jpn., 2023, 96, 938–942; (d)W. Kheli and C. K. Luscombe, Prog. Polym. Sci., 2024,151, 101804; (e) Y. Tanaka, A. Wake, D. Inoue andY. Moritomo, Jpn. J. Appl. Phys., 2024, 63, 014002.11 (a) A. Chapman, E. Ertekin, M. Kubota, A. Nagao,K. Bertsch, A. Macadre, T. Tsuchiyama, T. Masamura,S. Takaki, R. Komoda, M. Dadfarnia, B. Somerday,A. T. Staykov, J. Sugimura, Y. Sawae, T. Morita, H. Tanaka,© 2024 The Author(s). Published by the Royal Society of ChemistryK. Yagi, V. Niste, P. Saravanan, S. Onitsuka, K.-S. Yoon,S. Ogo, T. Matsushima, G. Tumen-Ulzii, D. Klotz,D. H. Nguyen, G. Harrington, C. Adachi, H. Matsumoto,L. Kwati, Y. Takahashi, N. Kosem, T. Ishihara,M. Yamauchi, B. Baran Saha, Md. A. Islam, J. Miyawaki,H. Sivasankaran, M. Kohno, S. Fujikawa, R. Selyanchyn,T. Tsuji, Y. Higashi, R. Kirchheim and P. Sofronis, Bull.Chem. Soc. Jpn., 2022, 95, 73–103; (b) A. Fukuoka, Bull.Chem. Soc. Jpn., 2023, 96, 1071–1076; (c) K. Kato,R. Matsui, Y. Xin, Y. Xu and T. Shirai, Appl. Surf. Sci.,2024, 664, 160280; (d) C. Xiao, J. Tian, Q. Chen andM. Hong, Chem. Sci., 2024, 15, 1570–1610; (e) C. Ayappan,R. Xing, X. Zhang, D. Luo, S. Liu and A. Fujishima, Coord.Chem. Rev., 2024, 515, 215960.12 (a) A. R. Pradipta, H. Michiba, A. Kubo, M. Fujii, T. Tanei,K. Morimoto, K. Shimazu and K. Tanaka, Bull. Chem. Soc.Jpn., 2022, 95, 421–426; (b) M. I. Setyawati, Q. Wang,N. Ni, J. K. Tee, K. Ariga, P. C. Ke, H. K. Ho, Y. Wang andD. T. Leong, Nat. Commun., 2021, 14, 4269; (c) T. Niwa,T. Tahara, C. E Chase, F. G. Fang, T. Nakaoka, S. Irie,E. Hayashinaka, Y. Wada, H. Mukai, K. Masutomi,Y. Watanabe, Y. Cui and T. Hosoya, Bull. Chem. Soc. Jpn.,2023, 96, 283–290; (d) T. Dong, M. Wang, J. Liu, P. Ma,S. Pang, W. Liu and A. Liu, Chem. Sci., 2023, 14, 6149–6206; (e) M. Yamagishi, Y. Kuze, S. Kobayashi,M. Nakashima, S. Morishima, T. Kawamata, J. Makiyama,K. Suzuki, M. Seki, K. Abe, K. Imamura, E. Watanabe,K. Tsuchiya, I. Yasumatsu, G. Takayama, Y. Hizukuri,K. Ito, Y. Taira, Y. Nannya, A. Tojo, T. Watanabe,S. Tsutsumi, Y. Suzuki and K. Uchimaru, Nature, 2024,627, 221–228.13 (a) L. T. B. Nguyen and M. Abe, Bull. Chem. Soc. Jpn., 2023,96, 899–906; (b) S. Mohanan, C. I. Sathish, T. J. Adams,S. Kan, M. Liang and A. Vinu, Bull. Chem. Soc. Jpn., 2023,96, 1188–1195; (c) W.-C. Geng, Z.-T. Jiang, S.-L. Chena andD.-S. Gu, Chem. Sci., 2024, 15, 7811–7823; (d) J. Borges,J. Zeng, X. Q. Liu, H. Chang, C. Monge, C. Garot, K. Ren,P. Machillot, N. E. Vrana, P. Lavalle, T. Akagi,M. Matsusaki, J. Ji, M. Akashi, J. F. Mano, V. Gribova andC. Picart, Adv. Healthcare Mater., 2024, 13, 2302713; (e)F. H. Nabila, R. Islam, I. Md Shimul, M. Moniruzzaman,R. Wakabayashi, N. Kamiya and M. Goto, Chem.Commun., 2024, 60, 4036–4039.14 (a) V. J. Sahayasheela, Z. Yu, Y. Hirose, G. N. Pandian,T. Bando and H. Sugiyama, Bull. Chem. Soc. Jpn., 2022, 95,693–699; (b) Y. Shang, J. Zeng, Z. Xie, N. Sasaki andM. Matsusaki, Bull. Chem. Soc. Jpn., 2022, 95, 1163–1168;(c) R. Hama, A. Ulziibayar, J. W. Reinhardt, T. Watanabe,J. Kelly and T. Shinoka, Biomolecules, 2023, 13, 280; (d)Y. Liang, L. Qiao, B. Qiaoa and B. Guo, Chem. Sci., 2023,14, 3091–3116; (e) J. Song, W. Lyu, K. Kawakami andK. Ariga, Nanoscale, 2024, 16, 13230–13246.15 (a) C. Liu, N. Morimoto, L. Jiang, S. Kawahara, T. Noritomi,H. Yokoyama, K. Mayumi and K. Ito, Science, 2021, 372,1078–1081; (b) M. Kaneko, T. Nakayama, H. Seki,S. Yamamoto, T. Uemura, K. Inoue, S. Hadano,S. Watanabe and Y. Niko, Bull. Chem. Soc. Jpn., 2023, 96,Chem. Sci., 2024, 15, 18715–18750 | 18745Chemical Science Review1760–1768; (c) H. Imahori, Bull. Chem. Soc. Jpn., 2023, 96,339–352; (d) K. Ariga, S. Akakabe, R. Sekiguchi,M. L. Thomas, Y. Takeoka, M. Rikukawa andM. Yoshizawa-Fujita, ACS Omega, 2024, 9, 22203–22212.16 (a) R. P. Feynman, Eng. Sci., 1960, 23, 32–36; (b) M. Roukes,Sci. Am., 2001, 285, 48–51.17 (a) Y. Sugimoto, P. Pou, M. Abe, P. Jelinek, R. Pérez,S. Morita and Ó. Custance, Nature, 2007, 446, 64–67; (b)A. Shiotari and Y. Sugimoto, Nat. Commun., 2017, 8,14313; (c) H. Hoelzel, S. Lee, K. Y. Amsharov, N. Jux,K. Harano, E. Nakamura and D. Lungerich, Nat. Chem.,2023, 15, 1444–1451.18 (a) P. Mishra, J. P. Hill, S. Vijayaraghavan, W. Van Rossom,S. Yoshizawa, M. Grisolia, J. Echeverria, T. Ono, K. Ariga,T. Nakayama, C. Joachim and T. Uchihashi, Nano Lett.,2015, 15, 4793–4798; (b) M. Hara, R. Oguri, S. Sarkar,S. Nagano and T. Seki, Bull. Chem. Soc. Jpn., 2022, 95,216–220; (c) H. Mitomo, C. Takeuchi, R. Sugiyama,K. Tamada and K. Ijiro, Bull. Chem. Soc. Jpn., 2022, 95,771–773.19 (a) K. Kimura, K. Miwa, H. Imada, M. Imai-Imada,S. Kawahara, J. Takeya, M. Kawai, M. Galperin andY. Kim, Nature, 2019, 570, 210–213; (b) H. Tokoro,K. Nakabayashi, S. Nagashima, Q. Song, M. Yoshikiyo andS. Ohkoshi, Bull. Chem. Soc. Jpn., 2022, 95, 538–552; (c)Y. Hashikawa and Y. Murata, Bull. Chem. Soc. Jpn., 2023,96, 943–967; (d) H. Ito, Y. Nakahira, N. Ishimatsu,Y. Goto, A. Yamashita, Y. Mizuguchi, C. Moriyoshi,T. Toyao, K. Shimizu, H. Oike, M. Enoki, N. C. Rosero-Navarro, A. Miura and K. Tadanaga, Bull. Chem. Soc. Jpn.,2023, 96, 1262–1268.20 K. Ariga, Nanoscale Horiz., 2021, 6, 364–378.21 (a) K. Ariga, Q. Ji, J. P Hill, Y. Bando and M. Aono, NPG AsiaMater., 2012, 4, e17; (b) K. Ariga, Q. Ji, W. Nakanishi,J. P. Hill and M. Aono, Mater. Horiz., 2015, 2, 406–413.22 K. Ariga, J. Li, J. Fei, Q. Ji and J. P. Hill, Adv. Mater., 2016, 28,1251–1286.23 (a) S. Datta, Y. Kato, S. Higashiharaguchi, K. Aratsu,A. Isobe, T. Saito, D. D. Prabhu, Y. Kitamoto,M. J. Hollamby, A. J. Smith, R. Dalgliesh, N. Mahmoudi,L. Pesce, C. Perego, G. M. Pavan and S. Yagai, Nature,2020, 583, 400–405; (b) K. Ariga, M. Nishikawa, T. Mori,J. Takeya, L. K. Shrestha and J. P. Hill, Sci. Technol. Adv.Mater., 2020, 20, 51–95; (c) G. Chen, F. Sciortino,K. Takeyasu, J. Nakamura, J. P. Hill, L. K. Shrestha andK. Ariga, Chem.–Asian J., 2022, 17, e202200756; (d)E. Mieda, Y. Morishima, T. Watanabe, H. Miyake andS. Shinoda, Bull. Chem. Soc. Jpn., 2023, 96, 538–544; (e)Y. Yamamoto, S. Kushida, D. Okada, O. Oki,H. Yamagishi and Hendra, Bull. Chem. Soc. Jpn., 2023, 96,702–710.24 (a) S. Horike, Bull. Chem. Soc. Jpn., 2023, 96, 887–898; (b)B. Ay, R. Takano and T. Ishida, Bull. Chem. Soc. Jpn., 2023,96, 1129–1138; (c) W. Wang, D. Chen, F. Li, X. Xiao andQ. Xu, Chem, 2024, 10, 86–133.25 (a) Y. Charles-Blin, T. Kondo, Y. Wu, S. Bandow andK. Awaga, Bull. Chem. Soc. Jpn., 2022, 95, 972–977; (b)18746 | Chem. Sci., 2024, 15, 18715–18750X. Wang, Y. Wada, T. Shimada, A. Kosaka, K. Adachi,D. Hashizume, K. Yazawa, H. Uekusa, Y. Shoji,T. Fukushima, M. Kawano and Y. Murakami, J. Am. Chem.Soc., 2024, 146, 1832–1838; (c) H. Mabuchi, T. Irie,J. Sakai, S. Das and Y. Negishi, Chem.–Eur. J., 2024, 30,e202303474.26 (a) Z.-Z. Pan, W. Lv, Q.-H. Yang and H. Nishihara, Bull.Chem. Soc. Jpn., 2022, 95, 611–620; (b) H. Matsune,R. Ikemizu, K. Shiomori, E. Muraoka, T. Yamamoto andM. Kishida, Bull. Chem. Soc. Jpn., 2023, 96, 813–815; (c)Y. Tu, Y. Inagaki and W. Setaka, J. Org. Chem., 2024, 89,6222–6229.27 (a) M. Aono and K. Ariga, Adv. Mater., 2016, 28, 989–992; (b)L. Cao, Y. Huang, B. Parakhonskiy and A. G. Skirtach,Nanoscale, 2022, 14, 15964–16002; (c) K. Ariga, Beilstein J.Nanotechnol., 2023, 14, 434–453.28 K. Ariga, X. Jia, J. Song, J. P. Hill, D. T. Leong, Y. Jia and J. Li,Angew. Chem., Int. Ed., 2020, 59, 15424–15446.29 (a) A. Nayak, S. Unayama, S. Tai, T. Tsuruoka, R. Waser,M. Aono, I. Valov and T. Hasegawa, Adv. Mater., 2018, 30,170326; (b) M. Eguchi, A. S. Nugraha, A. E. Rowan,J. Shapter and Y. Yamauchi, Adv. Sci., 2021, 8, 2100539; (c)X. Guan, Z. Li, X. Geng, Z. Lei, A. Karakoti, T. Wu,P. Kumar, J. Yi and A. Vinu, Small, 2023, 19, 2207181; (d)N. Shioya, T. Mori, K. Ariga and T. Hasegawa, Jpn. J. Appl.Phys., 2024, 63, 060102.30 (a) W. Nakanishi, K. Minami, L. K. Shrestha, Q. Ji, J. P. Hilland K. Ariga, Nano Today, 2014, 9, 378–394; (b) G. Chen,L. K. Shrestha and K. Ariga, Molecules, 2021, 26, 4636; (c)F. Attar, A. Sharma, B. Gupta and S. Karuturi, Adv. Sci.,2024, 11, 2308063; (d) P. A. Lu, Y. Hao, J. Q. Feng,M. R. Manikandan, C. Liu, F. Yang, P. F. Yang, R. Liu,X. F. Li, J. Shang, D. W. Zhang and X. W. Wang, Appl.Phys. A, 2024, 130, 118.31 (a) M. Komiyama, K. Yoshimoto, M. Sisido and K. Ariga,Bull. Chem. Soc. Jpn., 2017, 90, 967–1004; (b) Q. Liu, H. Li,B. Yu, Z. Meng, X. Zhang, J. Li and L. Zheng, Adv. Funct.Mater., 2022, 32, 2201196; (c) X. Shen, J. Song,C. Sevencan and D. T. Leong, Sci. Technol. Adv. Mater.,2023, 23, 199–224; (d) R. Xing, C. Yuan, W. Fan, X. Renand X. Yan, Sci. Adv., 2023, 9, eadd8105.32 (a) A. H. Khan, S. Ghosh, B. Pradhan, A. Dalui,L. K. Shrestha, S. Acharya and K. Ariga, Bull. Chem. Soc.Jpn., 2017, 90, 627–648; (b) J. Kim, J. H. Kim and K. Ariga,Joule, 2017, 1, 739–768; (c) G. Chen, S. K. Singh,K. Takeyasu, J. P. Hill, J. Nakamura and K. Ariga, Sci.Technol. Adv. Mater., 2023, 23, 413–423; (d) D. Bogachuk,J. Girard, S. Tilala, D. Martineau, S. Narbey, A. Verma,A. Hinsch, M. Kohlstädtac and L. Wagner, Nanoscale,2023, 15, 3130–3134.33 (a) S. Ishihara, J. Labuta, W. V. Rossom, D. Ishikawa,K. Minami, J. P. Hill and K. Ariga, Phys. Chem. Chem.Phys., 2014, 16, 9713–9746; (b) M. Komiyama, T. Mori andK. Ariga, Bull. Chem. Soc. Jpn., 2018, 91, 1075–1111; (c)G. Chen, B. N. Bhadra, L. Sutrisno, L. K. Shrestha andK. Ariga, Int. J. Mol. Sci., 2022, 23, 5454; (d)© 2024 The Author(s). Published by the Royal Society of ChemistryReview Chemical ScienceJ. V. Vaghasiya, C. C. Mayorga-Martinez and M. Pumera, npjFlexible Electron., 2023, 7, 26.34 (a) S. Xu, W.Wu, X. Zhou, H. Gu, X. Zhu, J. Zhai, S. Song andZ. Song, Appl. Phys. A, 2023, 129, 766; (b) T. Tsuchiya,T. Nakayama and K. Ariga, Appl. Phys. Express, 2022, 15,100101; (c) O. Azzaroni, E. Piccinini, G. Fenoy,W. Marmisollé and K. Ariga, Nanotechnology, 2023, 34,472001; (d) K. M. S. Dawngliana and S. Rai, Appl. Phys. A,2024, 130, 523.35 (a) M. Tipplook, H. Tanaka, T. Sudare, T. Hagio, N. Saitoand K. Teshima, ACS Appl. Mater. Interfaces, 2024, 16,7038–7046; (b) X. Yan, M. Chen, J. Wang, Z. Wang, R. Xin,D. Wu, Y. Song, S. Li, W. Zhu, C. Wang and Y. Mao,Chem. Eng. J., 2024, 495, 153431; (c) A. M. Sadanandan,J.-H. Yang, V. Devtade, G. Singh, N. P. Dharmarajan,M. Fawaz, J. M. Lee, E. Tavakkoli, C.-H. Jeon, P. Kumarand A. Vinu, Prog. Mater. Sci., 2024, 142, 101242; (d) Y. Lv,P. Li, X. Chen, D. Wang, M. Xiao, H. Song, J. Gao andY. Shang, J. Mol. Struct., 2024, 1297, 136961.36 (a) L. Sutrisno and K. Ariga, NPG Asia Mater., 2023, 15, 21;(b) J. Song, K. Kawakami and K. Ariga, Curr. Opin. ColloidInterface Sci., 2023, 65, 101702; (c) A. N. Resmi,S. Sivaselvam, C. R. Rekha, E. Papasouli,J. Kunnumpurathu, C. S. Praveen, E. N. Koukaras,M. Rerat, P. Karamanis and R. S. Jayasree, Appl. Mater.Today, 2024, 39, 102273; (d) A. M. de Almeida Jr,A. S. Ferreira, S. A. Camacho, L. G. Moreira, K. A. deToledo, O. N. Oliveira Jr and P. H. B. Aoki, ACS Appl.Mater. Interfaces, 2024, 16, 23742–23751.37 R. B. Laughlin and D. Pines, Proc. Natl. Acad. Sci. U. S. A.,2000, 97, 28–31.38 (a) K. Ariga and R. Fakhrullin, Bull. Chem. Soc. Jpn., 2022,95, 774–795; (b) K. Ariga, Bull. Chem. Soc. Jpn., 2024, 97,uoad001.39 (a) I. R. Vetter and A. Wittinghofer, Science, 2001, 294, 1299–1304; (b) P. Jordan, P. Fromme, H. T. Witt, O. Klukas,W. Saenger and N. Krauß, Nature, 2001, 411, 909–917; (c)K. N. Ferreira, T. M. Iverson, K. Maghlaoui, J. Barber andS. Iwata, Science, 2004, 303, 1831–1838.40 K. Ariga and Y. Yamauchi, Chem.–Asian J., 2020, 15, 718–728.41 (a) K. Ariga, Nanoscale, 2022, 14, 10610–10629; (b) K. Ariga,Molecules, 2024, 29, 3168; (c) K. Ariga, Materials, 2024, 17,271.42 (a) K. Ariga, Y. Yamauchi, T. Mori and J. P. Hill, Adv. Mater.,2013, 25, 6477–6512; (b) K. Ariga, Langmuir, 2020, 36, 7158–7180; (c) K. Ariga, Chem. Mater., 2023, 35(14), 5233–5254.43 (a) G. Rydzek, Q. Ji, M. Li, P. Schaaf, J. P. Hill, F. Boulmedaisand K. Ariga, Nano Today, 2015, 10, 138–167; (b) K. Ariga,Y. Lvov and G. Decher, Phys. Chem. Chem. Phys., 2022, 24,4097–4115; (c) K. Ariga, J. Song and K. Kawakami, Chem.Commun., 2024, 60, 2152–2167.44 K. Ariga, ChemNanoMat, 2023, 9, e202300120.45 (a) Y. Okawa and M. Aono, Nature, 2001, 409, 683–684; (b)Y. Okawa, S. K. Mandal, C. Hu, Y. Tateyama,S. Goedecker, S. Tsukamoto, T. Hasegawa,© 2024 The Author(s). Published by the Royal Society of ChemistryJ. K. Gimzewski and M. Aono, J. Am. Chem. Soc., 2011,133, 8227–8233.46 M. Nakaya, S. Tsukamoto, Y. Kuwahara, M. Aono andT. Nakayama, Adv. Mater., 2010, 22, 1622–1625.47 S. Kawai, O. Krejč́ı, T. Nishiuchi, K. Sahara, T. Kodama,R. Pawlak, E. Meyer, T. Kubo and A. S. Foster, Sci. Adv.,2020, 6, eaay8913.48 S. Kawai, H. Sang, L. Kantorovich, K. Takahashi, K. Nozakiand S. Ito, Angew. Chem., Int. Ed., 2020, 59, 10842–10847.49 (a) S. Clair and D. G. de Oteyza, Chem. Rev., 2019, 119, 4717–4776; (b) T. Kojima, C. Xie and H. Sakaguchi,ChemPlusChem, 2024, 89, e202300775; (c) R. Zuzak,M. Kumar, O. Stoica, D. Soler-Polo, J. Brabec, K. Pernal,L. Veis, R. Blieck, A. M. Echavarren, P. Jelinek andS. Godlewski, Angew. Chem., Int. Ed., 2024, 63, e202317091.50 (a) X. Li, X. Wang, L. Zhang, S. Lee and H. Dai, Science, 2008,319, 1229–1232; (b) A. L. Logrado, T. S. A. Cassiano, W. F. daCunha, R. Gargano, G. M. Silv and P. H. O. Neto, Phys.Chem. Chem. Phys., 2024, 26, 14948–14959.51 J.-J. Zhang, K. Liu, Y. Xiao, X. Yu, L. Huang, H.-J. Gao, J. Maand X. Feng, Angew. Chem., Int. Ed., 2023, 62, e202310880.52 N. Friedrich, J. Li, I. Pozo, D. Peña and J. I. Pascual, Adv.Mater., 2024, 2401955.53 A. J. Heinrich, C. P. Lutz, J. A. Gupta and D. M. Eigler,Science, 2002, 298, 1381–1387.54 W.-H. Soe, M. Kleinwächter, C. Kammerer, G. Rapenne andC. Joachim, J. Phys. Chem. C, 2020, 124(41), 22625–22630.55 K. H. A. Yeung, T. Kühne, F. Eisenhut, M. Kleinwächter,Y. Gisbert, R. Robles, N. Lorente, G. Cuniberti,C. Joachim, G. Rapenne, C. Kammerer and F. Moresco, J.Phys. Chem. Lett., 2020, 11, 6892–6899.56 (a) S. Negi, M. Hamori, H. Kitagishi and K. Kano, Bull.Chem. Soc. Jpn., 2022, 95, 1537–1545; (b) O. N. Oliveira Jr.,L. Caseli and K. Ariga, Chem. Rev., 2022, 122, 6459–6513;(c) S. Negi, M. Hamori, Y. Kubo, H. Kitagishi and K. Kano,Bull. Chem. Soc. Jpn., 2023, 96, 48–56; (d) M. Maeda,Y. Shioda and A. Fujimori, ChemistrySelect, 2024, 9,e202400063; (e) H. Tanaka, S. Hotta, T. Hinamoto,H. Sugimoto and M. Fujii, ACS Appl. Nano Mater., 2024, 7,2605–2613.57 (a) J. A. Allen, R. A. Halverson-Tamboli and M. M. Rasenick,Nat. Rev. Neurosci., 2007, 8, 128–140; (b) G. Li, X. Hu, P. Nie,D. Mang, S. Jiao, S. Zhang, S. R. Roy, S. Yukawa, S. Asahina,H. Sugasawa, W. Cortes, Z. Zhou and Y. Zhang, Nano Lett.,2021, 21, 747–755; (c) A. K. Nehr-Majoros, Á. Király,Z. Helyes and É. Sz}oke, Curr. Opin. Pharmacol., 2024, 75,102432.58 M. Zaborowska, D. Matyszewska and R. Bilewicz, Langmuir,2022, 38, 13888–13897.59 A. P. Fellows, B. John, M. Wolf and M. Thämer, Nat.Commun., 2024, 15, 3161.60 (a) X. Cha, K. Ariga and T. Kunitake, J. Am. Chem. Soc., 1996,118, 9545–9551; (b) K. Ariga, A. Kamino, H. Koyano andT. Kunitake, J. Mater. Chem., 1997, 7, 1155–1161.61 K. Ariga, A. Kamino, X. Cha and T. Kunitake, Langmuir,1999, 15, 3875–3885.Chem. Sci., 2024, 15, 18715–18750 | 18747Chemical Science Review62 (a) K. Ariga and T. Kunitake, Acc. Chem. Res., 1998, 31, 371–378; (b) K. Ariga, H. Ito, J. P. Hill and H. Tsukube, Chem. Soc.Rev., 2012, 41, 5800–5835; (c) K. Ariga, Phys. Chem. Chem.Phys., 2020, 22, 24856–24869.63 (a) M. Sakurai, H. Tamagawa, Y. Inoue, K. Ariga andT. Kunitake, J. Phys. Chem. B, 1997, 101(24), 4810–4816;(b) H. Tamagawa, M. Sakurai, Y. Inoue, K. Ariga andT. Kunitake, J. Phys. Chem. B, 1997, 101, 4817–4825.64 (a) K. Kurihara, K. Ohto, Y. Tanaka, Y. Aoyama andT. Kunitake, Thin Solid Films, 1989, 179, 21–26; (b)K. Kurihara, K. Ohto, Y. Tanaka, Y. Aoyama andT. Kunitake, J. Am. Chem. Soc., 1991, 113, 444–450.65 (a) Y. Ikeura, K. Kurihara and T. Kunitake, J. Am. Chem. Soc.,1991, 113, 7342–7350; (b) T. Michinobu, S. Shinoda,T. Nakanishi, J. P. Hill, K. Fujii, T. N. Player, H. Tsukubeand K. Ariga, Phys. Chem. Chem. Phys., 2011, 13, 4895–4900.66 (a) T. Kawahara, K. Kurihara and T. Kunitake, Chem. Lett.,1992, 21, 1839–1842; (b) W. Miao, X. Du and Y. Liang, J.Phys. Chem. B, 2003, 107, 13636–13642.67 (a) D. Y. Sasaki, K. Kurihara and T. Kunitake, J. Am. Chem.Soc., 1991, 113, 9685–9686; (b) D. Y. Sasaki, K. Kuriharaand T. Kunitake, J. Am. Chem. Soc., 1992, 114, 10994–10995.68 Y. Oishi, Y. Torii, T. Kato, M. Kuramori, K. Suehiro, K. Ariga,K. Taguchi, A. Kamino, H. Koyano and T. Kunitake,Langmuir, 1997, 13, 519–524.69 (a) D. Aoki and T. Takata, Polymer, 2017, 128, 276–296; (b)R. Kubota, Bull. Chem. Soc. Jpn., 2023, 96, 802–812; (c)K. Hamada, D. Shimoyama, T. Hirao and T. Haino, Bull.Chem. Soc. Jpn., 2023, 96, 621–627; (d) W.-L. Guan,J.-F. Chen, J. Liu, B. Shi, H. Yao, Y.-M. Zhang, T.-B. Weiand Q. Lin, Coord. Chem. Rev., 2024, 507, 215717.70 H. Koyano, K. Yoshihara, K. Arigo, T. Kunitake, Y. Oishi,O. Kawano, M. Kuramori and K. Suehiro, Chem. Commun.,1996, 1769–1770.71 V. Marchi-Artzner, F. Artzner, O. Karthaus, M. Shimomura,K. Ariga, T. Kunitake and J.-M. Lehn, Langmuir, 1998, 14,5164–5171.72 S. Yamazaki, M. Harada, Y. Watanabe, R. Lang, T. Kato,O. Haba, K. Fukushima and J. Kumaki, Langmuir, 2023,39, 5486–5494.73 (a) S. S. Babu, V. K. Praveen and A. Ajayaghosh, Chem. Rev.,2014, 114, 1973–2129; (b) S. Cherumukkil, G. Das,R. P. N. Tripathi, G. V. PavanKumar, S. Varughese andA. Ajayaghosh, Adv. Funct. Mater., 2022, 32, 2109041; (c)Y. Sekine and T. Nankawa, Bull. Chem. Soc. Jpn., 2023, 96,1150–1155.74 K. Sakakibara, P. Chithra, B. Das, T. Mori, M. Akada,J. Labuta, T. Tsuruoka, S. Maji, S. Furumi, L. K. Shrestha,J. P. Hill, S. Acharya, K. Ariga and A. Ajayaghosh, J. Am.Chem. Soc., 2014, 136, 8548–8551.75 (a) K. Ariga, Q. Ji, M. J. McShane, Y. M. Lvov, A. Vinu andJ. P. Hill, Chem. Mater., 2012, 24, 728–737; (b) K. Ariga,T. Mor and J. P. Hill, Adv. Mater., 2012, 24, 158–176.76 (a) K. Ariga, T. Mori, W. Nakanishi and J. P. Hill, Phys.Chem. Chem. Phys., 2017, 19, 23658–23676; (b) K. Ariga,Curr. Opin. Colloid Interface Sci., 2023, 63, 101656; (c)T. Mori, Sci. Technol. Adv. Mater., 2024, 25, 2334667.18748 | Chem. Sci., 2024, 15, 18715–1875077 I. C. Lee, C. W. Frank, T. Yamamoto, H.-R. Tseng,A. H. Flood, J. F. Stoddart and J. O. Jeppesen, Langmuir,2004, 20, 5809–5828.78 (a) K. Ariga, Chem. Sci., 2020, 11, 10594–10604; (b) K. Ariga,J. Song and K. Kawakami, Phys. Chem. Chem. Phys., 2024,26, 13532–13560.79 (a) K. Ariga, K. Minami, M. Ebara and J. Nakanishi, Polym.J., 2016, 48, 371–389; (b) L. K. Shrestha, T. Mori andK. Ariga, Curr. Opin. Colloid Interface Sci., 2018, 35, 68–80.80 (a) K. Ariga, Y. Terasaka, D. Sakai, H. Tsuji and J. Kikuchi, J.Am. Chem. Soc., 2000, 122, 7835–7836; (b) K. Ariga,T. Nakanishi, Y. Terasaka, H. Tsuji, D. Sakai andJ. Kikuchi, Langmuir, 2005, 21, 976–981.81 T. Michinobu, S. Shinoda, T. Nakanishi, J. P. Hill, K. Fujii,T. N. Player, H. Tsukube and K. Ariga, J. Am. Chem. Soc.,2006, 128, 14478–14479.82 T. Mori, K. Okamoto, H. Endo, J. P. Hill, S. Shinoda,M. Matsukura, H. Tsukube, Y. Suzuki, Y. Kanekiyo andK. Ariga, J. Am. Chem. Soc., 2010, 132, 12868–12870.83 K. Sakakibara, L. A. Joyce, T. Mori, T. Fujisawa,S. H. Shabbir, J. P. Hill, E. V. Anslyn and K. Ariga, Angew.Chem., Int. Ed., 2012, 51, 9643–9646.84 (a) J. M. Lehn, Angew. Chem., Int. Ed. Engl., 1988, 27, 89–112;(b) D. J. Cram, Angew. Chem., Int. Ed. Engl., 1988, 27, 1009–1020; (c) C. J. Pedersen, Angew. Chem., Int. Ed. Engl., 1988,27, 1021–1027; (d) X. Y. Zhu, X. N. Yang, H. Wu, Z. Taoand X. Xiao, Bull. Chem. Soc. Jpn., 2022, 95, 116–120; (e)A. Muranaka, H. Ban, M. Naito, S. Miyagawa, M. Ueda,S. Yamamoto, M. Harada, H. Takaya, M. Kimura,N. Kobayashi, M. Uchiyama and Y. Tokunaga, Bull. Chem.Soc. Jpn., 2022, 95, 1428–1437.85 (a) S. Shinkai, T. Ogawa, T. Nakaji, Y. Kusano andO. Nanabe, Tetrahedron Lett., 1979, 20, 4569–4572; (b)S. Shinkai, T. Minami, Y. Kusano and O. Manabe, J.Chem. Soc., Perkin Trans. 1, 1982, 2735–2739.86 (a) J.-P. Sauvage, Angew. Chem., Int. Ed., 2017, 56, 11080–11093; (b) J. F. Stoddart, Angew. Chem., Int. Ed., 2017, 56,11094–11125; (c) B. L. Feringa, Angew. Chem., Int. Ed.,2017, 56, 11060–11078.87 (a) K. Ariga, ChemNanoMat, 2020, 6, 870–880; (b) K. Ariga,Small Methods, 2022, 6, 2101577.88 Y. Tabe and H. Yokoyama, Nat. Mater., 2003, 2, 806–809.89 P. Milczarczyk-Piwowarczyk, A. Żywociński, K. Noworytaand R. Hołyst, Langmuir, 2008, 24, 12354–12363.90 Y. Tabe, T. Yamamoto and H. Yokoyama, New J. Phys., 2003,5, 65.91 (a) R. Makiura and O. Konovalov, Sci. Rep., 2013, 3, 2506; (b)Z. Wang, L. S. Walter, M. Wang, P. St. Petkov, B. Liang,H. Qi, N. N. Nguyen, M. Hambsch, H. Zhong, M. Wang,S. W. Park, L. Renn, K. Watanabe, T. Taniguchi,S. C. B. Mannsfeld, T. Heine, U. Kaiser, S. Zhou,R. T. Weitz, X. Feng and R. Dong, J. Am. Chem. Soc., 2021,143, 13624–13632.92 (a) K. Dey, M. Pal, K. C. Rout, S. Kunjattu H., A. Das,R. Mukherjee, U. K. Kharul and R. Banerjee, J. Am. Chem.Soc., 2017, 139, 13083–13091; (b) D. Zhou, X. Tan, H. Wu,L. Tian and M. Li, Angew. Chem., Int. Ed., 2019, 58, 1376–© 2024 The Author(s). Published by the Royal Society of ChemistryReview Chemical Science1381; (c) A. Giri, G. Shreeraj, T. K. Dutta and A. Patra, Angew.Chem., Int. Ed., 2023, 62, e202219083.93 (a) X. Zhang, J. Zhao, Q. Zhu, N. Chen, M. Zhang andQ. Pan, ACS Appl. Mater. Interfaces, 2011, 3, 2630–2636; (b)K. Ariga, Micromachines, 2023, 14, 25.94 (a) R. Makiura, Coord. Chem. Rev., 2022, 469, 214650; (b)T. Ohata, K. Tachimoto, K. J. Takeno, A. Nomoto,T. Watanabe, I. Hirosawa and R. Makiura, Bull. Chem. Soc.Jpn., 2023, 96, 274–282.95 R. Makiura, S. Motoyama, Y. Umemura, H. Yamanaka,O. Sakata and H. Kitagawa, Nat. Mater., 2010, 9, 565–571.96 I. Aratani, Y. Horii, D. Takajo, Y. Kotani, H. Osawa andT. Kajiwara, J. Mater. Chem. C, 2023, 11, 2082–2088.97 M. Matsumoto, L. Valentino, G. M. Stiehl, H. B. Balch,A. R. Corcos, F. Wang, D. C. Ralph, B. J. Mariñas andW. R. Dichtel, Chem, 2018, 4, 308–317.98 N. Huang, L. Zhai, D. E. Coupry, M. A. Addicoat,K. Okushita, K. Nishimura, T. Heine and D. Jiang, Nat.Commun., 2016, 7, 12325.99 B. Zhang, H. Mao, R. Matheu, J. A. Reimer, S. A. Alshmimri,S. Alshihri and O. M. Yaghi, J. Am. Chem. Soc., 2019, 141,11420–11424.100 (a) A. Barbot, H. Tan, M. Power, F. Seichepine andG.-Z. Yang, Sci. Robot., 2019, 4, eaax8336; (b) L. Wang,L. Chen, X. Zheng, Z. Yu, W. Lv, M. Sheng, L. Wang,P. Nie, H. Li, D. Guan and H. Cui, Small, 2022, 18,2203872; (c) W. Yang, X. Wang, Z. Wang, Z. Yuan, Z. Geand H. Yu, So Matter, 2023, 19, 913–920.101 G. Zhao, T. H. Seah and M. Pumera, Chem.–Eur. J., 2011, 17,12020–12026.102 A. Jancik-Prochazkova, C. C. Mayorga-Martinez, J. Vyskočiland M. Pumera, ACS Appl. Mater. Interfaces, 2022, 14,45545–45552.103 (a) M. Hieda, K. Tsujimura, M. Kinoshita andN. Matsumori, Bull. Chem. Soc. Jpn., 2022, 95, 1753–1759;(b) S. Li, G. S. P. Mok and Y. Dai, Adv. Drug Delivery Rev.,2023, 202, 115110; (c) T. Sakuragi and S. Nagata, Nat. Rev.Mol. Cell Biol., 2023, 24, 576–596.104 (a) D. Y. Zhang and G. Seelig, Nat. Chem., 2011, 3, 103–113;(b) N. C. Seeman and H. F. Sleiman, Nat. Rev. Mater., 2018,3, 17068; (c) S. Kosara, R. Singh and D. Bhatia, NanoscaleAdv., 2024, 6, 386–401.105 (a) B. Bechinger, J. Membr. Biol., 1997, 156, 197–211; (b)C. Lang, D. Ye, W. Song, C. Yao, Y. Tu, C. Capparelli,J. A. LaNasa, M. A. Hickner, E. W. Gomez, E. D. Gomez,R. J. Hickey and M. Kumar, ACS Nano, 2019, 13, 8292–8302; (c) Y. Cui, A. Taguchi, H. Shida, S. Konno,K. Takayama, A. Taniguchi and Y. Hayashi, Bull. Chem.Soc. Jpn., 2022, 95, 1156–1162; (d) J. H. Viles, Angew.Chem., Int. Ed., 2023, 62, e202215785.106 H. Joshi and P. K. Maiti, Nucleic Acids Res., 2018, 46, 2234–2242.107 (a) M. G. L. van den Heuvel and C. Dekker, Science, 2007,317, 333–336; (b) S. Nowroz, S. R. Nasrin, A. Md R. Kabir,T. Yamashita, T. Kusumoto, J. Taira, M. Tani,M. Ichikawa, K. Sada and A. Kakugo, Biochem. Biophys.© 2024 The Author(s). Published by the Royal Society of ChemistryRes. Commun., 2024, 706, 149761; (c) D. H. Utomo andM. Kita, Bull. Chem. Soc. Jpn., 2023, 96, 120–126.108 R. Ibusuki, T. Morishita, A. Furuta, S. Nakayama,M. Yoshio, H. Kojima, K. Oiwa and K. Furuta, Science,2022, 375, 1159–1164.109 Y. Sato, M. Endo, M. Morita, M. Takinoue, H. Sugiyama,S. Murata, S.-i. M. Nomura and Y. Suzuki, Adv. Mater.Interfaces, 2018, 5, 1800437.110 C. M. A. Journot, V. Ramakrishna, M. I. Wallace andA. J. Turbereld, ACS Nano, 2019, 13, 9973–9979.111 J. Yang, K. Jahnke, L. Xin, X. Jing, P. Zhan, A. Peil, A. Griffo,M. Škugor, D. Yang, S. Fan, K. Göpfrich, H. Yan, P. Wangand N. Lium, Nano Lett., 2023, 23, 6330–6336.112 (a) J. Kikuchi, K. Ariga, T. Miyazaki and K. Ikeda, Chem.Lett., 1999, 28, 253–254; (b) J. Kikuchi, K. Ariga andK. Ikeda, Chem. Commun., 1999, 547–548.113 K. Fukuda, Y. Sasaki, K. Ariga and J. Kikuchi, J. Mol. Catal.B: Enzym., 2001, 11, 971–976.114 (a) Q. He, Y. Cuia and J. Li, Chem. Soc. Rev., 2009, 38, 2292–2303; (b) Y. Jia and J. Li, Nat. Rev. Chem, 2019, 3, 361–374; (c)Y. Jia and J. Li, Acc. Chem. Res., 2019, 52, 1623–1631.115 Z. Li, X. Xu, F. Yu, J. Fei, Q. Li, M. Dong and J. Li, Angew.Chem., Int. Ed., 2022, 61, e202116220.116 Z. Li, F. Yu, X. Xu, T. Wang, J. Fei, J. Hao and J. Li, J. Am.Chem. Soc., 2023, 145, 20907–20912.117 Z. Dong, J. Fei, T. Wang and J. Li, J. Colloid Interface Sci.,2023, 638, 76–83.118 X. Xu, J. Fei, Y. Xu, G. Li, W. Dong, H. Xue and J. Li, Angew.Chem., Int. Ed., 2021, 60, 7617–7620.119 T. Wang, J. Fei, Z. Dong, F. Yu and J. Li, Angew. Chem., Int.Ed., 2024, 63, e202319116.120 M. Ishii, Y. Yamashita, S. Watanabe, K. Ariga and J. Takeya,Nature, 2023, 622, 285–291.121 (a) M. Sytnyk, M. Jakešová, M. Litviňuková, O. Mashkov,D. Kriegner, J. Stangl, J. Nebesá̌rová, F. W. Fecher,W. Schöerger, N. S. Saricici, R. Schindl, W. Heiss andE. D. Głowacki, Nat. Commun., 2017, 8, 91; (b) J. Song,X. Jia, K. Minami, J. P. Hill, J. Nakanishi, L. K. Shresthaand K. Ariga, ACS Appl. Nano Mater., 2020, 3, 6497–6506.122 (a) X. Jia, J. Chen, W. Lv, H. Li and K. Ariga, Cell Rep. Phys.Sci., 2023, 4, 101251; (b) W. Hu, J. Shi, W. Lv, X. Jia andK. Ariga, Sci. Technol. Adv. Mater., 2023, 23, 393–412; (c)T. Ueki, K. Uto, S. Yamamoto, R. Tamate, Y. Kamiyama,X. Jia, H. Noguchi, K. Minami, K. Ariga, H. Wang andJ. Nakanishi, Adv. Mater., 2024, 36, 2310105.123 X. Jia, K. Minami, K. Uto, A. C. Chang, J. P. Hill, T. Ueki,J. Nakanishi and K. Ariga, Small, 2019, 15, 1804640.124 W. Lyu, W. Hu, J. Shi, J. Chen, J. Song, Q. Zhang, X. Yuan,D. Li, J. Nakanishi and X. Jia, Adv. Healthcare Mater.,2023, 12, 2300666.125 X. Jia, K. Minami, K. Uto, A. C. Chang, J. P. Hill, J. Nakanishiand K. Ariga, Adv. Mater., 2019, 32, 1905942.126 X. Jia, J. Song, W. Lv, J. P. Hill, J. Nakanishi and K. Ariga,Nat. Commun., 2022, 13, 3110.127 (a) J. Song, C. Yuan, T. Jiao, R. Xing, M. Yang, D. J. Adamsand X. Yan, Small, 2020, 16, 1907309; (b) Y. Jia, X. Yan andJ. Li, Angew. Chem., Int. Ed., 2022, 61, e202207752; (c)Chem. Sci., 2024, 15, 18715–18750 | 18749Chemical Science ReviewR. Miyake, K. Minagawa and Y. Sato, Bull. Chem. Soc. Jpn.,2023, 96, 103–109; (d) R. Chang, L. Zhao, R. Xing, J. Liand X. Yan, Chem. Soc. Rev., 2023, 52, 2688–2712; (e)H. Inaba, Y. Hori, A. Md R. Kabir, A. Kakugo, K. Sada andK. Matsuura, Bull. Chem. Soc. Jpn., 2023, 96, 1082–1087;(f) C. Yuan, Q. Li, R. Xing, J. Li and X. Yan, Chem, 2023, 9,2425–2445.128 (a) R. D. Piner, J. Zhu, F. Xu, S. Hong and C. A. Mirkin,Science, 1999, 283, 661–663; (b) G. Liu, S. H. Petrosko,Z. Zheng and C. A. Mirkin, Chem. Rev., 2020, 120, 6009–6047.129 (a) E. T. Castellana and P. S. Cremer, Surf. Sci. Rep., 2006,61, 429–444; (b) C. Ausilio, C. Lubrano, D. Rana,18750 | Chem. Sci., 2024, 15, 18715–18750G. M. Matrone, U. Bruno and F. Santoro, Adv. Sci., 2024,11, 2305860.130 (a) N. Saito, A. Nawachi, Y. Kondo, J. Choi, H. Morimotoand T. Ohshima, Bull. Chem. Soc. Jpn., 2023, 96, 465–474;(b) R. Hikichi, Y. Tokura, Y. Igarashi, H. Imai andY. Oaki, Bull. Chem. Soc. Jpn., 2023, 96, 766–774; (c)S. Horikawa, K. Suzuki, K. Motojima, K. Nakano,M. Nagaya, H. Nagashima, H. Kaneko and M. Aizawa,Materials, 2024, 17, 571; (d) N. Ishihara, G. Chikatani,H. Nishijima, H. Tabata, Y. Hase, Y. Mukouyama,S. Nakanishi and S. Mukaida, Chem. Lett., 2024, 53,upae087.131 W. Chaikittisilp, Y. Yamauchi and K. Ariga, Adv. Mater.,2022, 34, 2107212.© 2024 The Author(s). Published by the Royal Society of Chemistry Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Lateral nanoarchitectonics from nano to life: ongoing challenges in interfacial chemical science Button1: